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What changed in Akebia Therapeutics, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Akebia Therapeutics, Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+1548 added−1545 removedSource: 10-K (2025-03-13) vs 10-K (2024-03-14)

Top changes in Akebia Therapeutics, Inc.'s 2024 10-K

1548 paragraphs added · 1545 removed · 501 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

63 edited+46 added−676 removed51 unchanged
Biggest changeIDA: results from low levels of iron due to abnormal iron absorption and utilization in patients with CKD. Auryxia Auryxia is an iron-based, non-calcium, non-chewable, orally-administered tablet approved and marketed in the U.S., Japan and Taiwan for the treatment of hyperphosphatemia in adult patients with dialysis dependent CKD and for the treatment of IDA in adult patients with NDD-CKD.
Biggest changeAuryxia® (ferric citrate) is an orally administered medicine approved and marketed in the U.S. for two indications: (1) the control of serum phosphorus levels in adult patients with dialysis dependent chronic kidney disease, or DD-CKD , and (2) the treatment of iron deficiency anemia, or IDA , in adult patients with non-dialysis-dependent chronic kidney disease, or NDD-CKD .
Analysis of MACE events conducted by Akebia in the PRO 2 TECT program revealed that the greater number of MACE events observed among vadadustat patients as compared to the active comparator was primarily related to an excess of non-cardiovascular death and death-of-unknown-cause in regions outside of the U.S. where significant differences in treatment patterns for NDD-CKD patients were observed.
Analysis of MACE events conducted by the Company in the PRO 2 TECT program revealed that the greater number of MACE events observed among vadadustat patients as compared to the active comparator was primarily related to an excess of non-cardiovascular death and death-of-unknown-cause in regions outside of the U.S. where significant differences in treatment patterns for NDD-CKD patients were observed.
Vadadustat also achieved the primary safety endpoint of the INNO 2 VATE program, defined as non-inferiority of vadadustat versus darbepoetin alfa in time to first occurrence of MACE across both INNO 2 VATE studies.
Vadadustat also achieved the primary safety endpoint of the INNO 2 VATE program, defined as non-inferiority of vadadustat versus darbepoetin alfa in time to first occurrence of MACE across both INNO 2 VATE studies. Vadadustat achieved the INNO 2 VATE program’s primary safety endpoint of non-inferiority for MACE.
NI for the primary safety analysis was achieved if the upper bound of the 95% confidence interval for the hazard ratio of vadadustat to darbepoetin alfa did not exceed the pre-specified NI margin.
NI for the primary safety analysis was achieved if the upper bound of the 95% confidence interval for the hazard ratio, or HR , of vadadustat to darbepoetin alfa did not exceed the pre-specified NI margin.
Phosphate binders need to be taken with meals and snacks, and it is not uncommon for DD-CKD patients to be prescribed as many as 12 or more phosphate binder pills per day, among other medications. Patients taking phosphate binders also experience gastrointestinal tolerability issues.
Phosphate binders need to be taken with meals and snacks, and it is not uncommon for CKD patients receiving dialysis to be prescribed as many as 12 or more phosphate binder pills per day, among other medications. Patients taking phosphate binders also experience gastrointestinal tolerability issues.
The upper bound of the 95% confidence interval of the Hazard Ratio (HR) was above the pre-specified NI margin of 1.25 for primary MACE analysis (HR 1.17, 95% CI: 1.01, 1.36).
The upper bound of the 95% confidence interval of the HR was above the pre-specified NI margin of 1.25 for primary MACE analysis (HR 1.17, 95% CI: 1.01, 1.36).
IV iron is viewed as an effective treatment; however, like other intravenous medicines, it is logistically difficult to administer in an office setting, where NDD-CKD patients are more often treated. Commercialization We market Auryxia in the U.S. through our well-established, nephrology-focused sales force and commercial organization.
IV iron is viewed as an effective treatment; however, like other intravenous medicines, it is logistically difficult to administer in an office setting, where NDD-CKD patients are more often treated. Auryxia – An oral treatment for hyperphosphatemia and iron deficiency anemia We market Auryxia in the U.S. through our well-established, nephrology-focused sales force and commercial organization.
We have entered into supply agreements with STA Pharmaceutical Hong Kong Limited, or STA , for the manufacture of vadadustat drug substance and drug product for commercial use.
We have entered into supply agreements with STA Pharmaceutical Hong Kong Limited, or STA , for the manufacture of Vafseo drug substance and drug product for commercial use and Patheon Inc. for the manufacture of Vafseo drug product for commercial use.
MO 2 DIFY Study Primary and Secondary Efficacy Endpoint Results In the MO 2 DIFY study, the vadadustat once-daily, or QD , treatment (starting dose: 300 or 450 mg) achieved the primary efficacy endpoint of the mean change in Hb from baseline to the primary evaluation period (weeks 20-26) compared to darbepoetin alfa in adult patients on hemodialysis, demonstrating non-inferiority to darbepoetin alfa based on a non-inferiority margin of -0.75 g/dL.
MO 2 DIFY Study Primary and Secondary Efficacy Endpoint Results Akebia Therapeutics, Inc. | Form 10-K | Page 13 Table of Contents In the MO 2 DIFY study, the vadadustat once-daily, or QD , treatment (starting dose: 300 or 450 mg) achieved the primary efficacy endpoint of the mean change in Hb from baseline to the primary evaluation period (weeks 20-26) compared to darbepoetin alfa in adult patients on hemodialysis, demonstrating non-inferiority to darbepoetin alfa based on a non-inferiority margin of -0.75 g/dL.
In adults with functioning kidneys, normal serum phosphorus levels are 2.5 to 4.5 mg/dL. In adults with DD-CKD, elevated phosphorus levels, or hyperphosphatemia, can be associated with adverse effects, including increased risk for cardiovascular disease, bone disease and death. Phosphate binders and phosphate inhibitors are the only interventions marketed for the treatment of hyperphosphatemia. According to the U.S.
In adults with DD-CKD, elevated phosphorus levels, or hyperphosphatemia, can be associated with adverse effects, including increased risk for cardiovascular disease, bone disease and death. Phosphate binders and phosphate inhibitors are the only interventions marketed for the treatment of hyperphosphatemia. According to the U.S.
The incidence of TEAEs during the Correction study in the vadadustat-treated patients was 90.9%, and 91.6% in darbepoetin alfa-treated patients.
The incidence of treatment emergent adverse events, or TEAEs , during the Correction study in the vadadustat-treated patients was 90.9%, and 91.6% in darbepoetin alfa-treated patients.
Top-line Results from Global Phase 3 PRO 2 TECT Program within NDD-CKD Adult Patients The two PRO 2 TECT studies ( Correction and Conversion ), which collectively enrolled 3,476 patients, evaluated the efficacy and safety of vadadustat for the treatment of anemia due to CKD in NDD-CKD adult patients.
Top-line Results from Global Phase 3 PRO 2 TECT Program within NDD-CKD Adult Patients Akebia Therapeutics, Inc. | Form 10-K | Page 11 Table of Contents The two PRO 2 TECT studies (Correction and Conversion), which collectively enrolled 3,476 patients, evaluated the efficacy and safety of vadadustat for the treatment of anemia due to CKD in NDD-CKD adult patients.
On March 29, 2022, the FDA issued a complete response letter, or CRL , to our NDA. The FDA concluded that the data in the NDA did not support a favorable benefit-risk assessment of vadadustat for dialysis and non-dialysis patients.
We initially submitted a New Drug Application, or NDA , to the FDA for vadadustat in March 2021 and in March 2022, the FDA issued a complete response letter, or CRL , to our NDA. The FDA concluded that the data in the NDA did not support a favorable benefit-risk assessment of vadadustat for dialysis and non-dialysis patients.
Safety Results Akebia Therapeutics, Inc. | Form 10-K | Page 15 Table of Content s Among all randomized patients who received at least one dose of the study medication (n=317), 84.8% and 84.6% of patients in the vadadustat QD and TIW groups, respectively, experienced any TEAEs, compared to 80.6% in the darbepoetin alfa group.
Safety Results Among all randomized patients who received at least one dose of the study medication (n=317), 84.8% and 84.6% of patients in the vadadustat QD and TIW groups, respectively, experienced any TEAEs, compared to 80.6% in the darbepoetin alfa group.
The incidence of TEAEs during the Conversion study in vadadustat treated patients was 89.1% and 87.7% in darbepoetin alfa-treated patients. During the study, the most common TEAEs reported in vadadustat/darbepoetin alfa-treated patients were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract infection (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%).
During the study, the most common TEAEs reported in vadadustat/darbepoetin alfa-treated patients were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract Akebia Therapeutics, Inc. | Form 10-K | Page 12 Table of Contents infection (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%).
Data from our preclinical studies of AKB-10108 in mouse and rat models of ROP showed significant improvements in retinal development under hyperoxic conditions, as well as significant reductions in abnormal blood vessel growth after returning to normal oxygen levels.
Data from our preclinical studies of AKB-10108 in mouse and rat models of ROP showed significant improvements in retinal development under hyperoxic conditions, as well as significant reductions in abnormal blood vessel growth after returning to normal oxygen levels. Clinical Development Programs Below is a summary of the clinical development work completed for vadadustat.
The mortality rate among patients with ARDS in the study was: 34.9% with mild ARDS; 40.3% with moderate ARDS and 46.1% with severe ARDS. There are currently no treatments available for ARDS except for supportive care.
The mortality rate among patients with ARDS in the study was: 34.9% with mild ARDS; 40.3% with moderate ARDS and 46.1% with severe ARDS. There are currently no treatments Akebia Therapeutics, Inc. | Form 10-K | Page 10 Table of Contents available for ARDS except for supportive care.
We have selected two additional HIF molecules for preclinical development: AKB-9090, for use in an acute care setting, potentially for acute kidney disease, or AKI , or acute respiratory distress syndrome, or ARDS , and AKB-10108 for retinopathy of prematurity, or ROP , in neonates.
We have selected two additional HIF molecules for preclinical development: AKB-9090, potentially for cardiac surgery-related acute kidney injury, or CS-AKI , or acute respiratory distress syndrome, or ARDS , and AKB-10108 for retinopathy of prematurity, or ROP , in neonates.
Akebia Therapeutics, Inc. | Form 10-K | Page 13 Table of Content s Primary Safety Major Adverse Cardiovascular Events (MACE) Endpoint Result The PRO 2 TECT program ( Correction and Conversion studies) (n=3,471): • Primary Safety MACE Endpoint Result : Vadadustat did not meet the PRO2TECT program's primary safety endpoint of non-inferiority for MACE.
Primary Safety Major Adverse Cardiovascular Events (MACE) Endpoint Result The PRO 2 TECT program (Correction and Conversion studies) (n=3,471): • Primary Safety MACE Endpoint Result : Vadadustat did not meet the PRO2TECT program's primary safety endpoint of non-inferiority for MACE.
In a final ESRD PPS rule published in November 2018, CMS confirmed that it will expand the Transitional Drug Add-on Payment Adjustment, or TDAPA , to all new dialysis drugs approved by the FDA after January 1, 2020.
In a final ESRD PPS rule published in November 2018, Centers for Medicare & Medicaid Services, or CMS, confirmed that it will expand the TDAPA to all new dialysis drugs approved by the FDA after January 1, 2020.
Renal Data System 2022 Annual Data Report, there were nearly 558,000 patients in the U.S. on dialysis in 2020, of which 86% were on in-center hemodialysis and the remainder on home dialysis, which includes both peritoneal dialysis and home hemodialysis.
Left untreated, anemia accelerates the overall deterioration of patient health with increased morbidity and mortality. According to the U.S. Renal Data System 2022 Annual Data Report, there were nearly 558,000 patients in the U.S. on dialysis in 2020, of which 86% were on in-center hemodialysis and the remainder on home dialysis, which includes both peritoneal dialysis and home hemodialysis.
Item 1. Business Overview We are a fully integrated, commercial-stage biopharmaceutical company committed to addressing patients’ unmet needs. We have built a business focused on developing and commercializing innovative therapeutics that we believe serve as a foundation for future growth.
Item 1. Business Overview We are a fully integrated biopharmaceutical company with two commercial products for patients impacted by kidney disease. We have built a business focused on developing and commercializing innovative therapeutics that we believe serve as a foundation for future growth.
Stabilization of HIF by prolyl hydroxylase inhibition leads to the release of erythropoietin, increased extracellular adenosine signaling, increased glycolytic activity and decreased inflammation in lung epithelial cells that promote resolution of the lung injury. Vadadustat lessened the severity of COVID-19 pneumonia in a clinical trial (NCT04478071) and improved outcomes in animal models of acute lung injury.
Stabilization of HIF by prolyl hydroxylase inhibition leads to the release of erythropoietin, increased extracellular adenosine signaling, increased glycolytic activity and decreased inflammation in lung epithelial cells that promote resolution of the lung injury.
The current standard of care for anemia due to CKD is treatment by injectable recombinant human erythropoiesis-stimulating agents, or ESAs , such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa) or Mircera® (methoxy polyethylene glycol-epoetin beta), or blood transfusion.
The current standard of care for anemia due to CKD is treatment by injectable recombinant human ESAs such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa) or Mircera® (methoxy polyethylene glycol-epoetin beta), or blood transfusion. When administered to a patient, injectable ESAs provide supraphysiological levels of exogenous EPO to stimulate production of red blood cells, or RBCs .
Manufacturing and Supply Overview We neither own nor operate, and currently have no plans to own or operate, any manufacturing or distribution facilities. We rely on third-party contract manufacturing organizations, or CMOs , to produce all of our preclinical, clinical and commercial supply, and third-party distributors to distribute Auryxia.
We rely on third-party contract manufacturing organizations, or CMOs , to produce all of our preclinical, clinical and commercial supply, and third-party distributors to distribute Auryxia and Vafseo.
We plan to conduct a trial with vadadustat for the treatment of ARDS due to suspected aspiration, pathogen-associated pneumonia, or sepsis in hospitalized patients, which could further validate the therapeutic approach for HIF stabilization in ARDS and provide clinical data to support clinical development of an alternative HIF-based molecule such as AKB-9090 for ARDS.
Our plan is to first study HIF activity in vadadustat for the treatment of ARDS due to suspected aspiration, pathogen-associated pneumonia, or sepsis in hospitalized patients, which could provide clinical data from an investigator-initiated trial, and then to use these findings to support clinical development of an alternative HIF-based molecule such as AKB 9090 for ARDS.
Averoa SAS, or Averoa , has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA , Turkey, Switzerland and the United Kingdom, or UK . We expect Averoa will apply for marketing authorization for ferric citrate in Europe.
Averoa SAS, or Averoa , has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA , Turkey, Switzerland, the UK, the Balkans and certain countries in Eastern Europe and the Middle East. Averoa applied for marketing authorization for ferric citrate in Europe in April 2024.
In the U.S., CKD significantly impacts the U.S. healthcare system, potentially affecting about 37 million patients and costing Medicare nearly $125.0 billion annually for treating Medicare beneficiaries with CKD or end-stage renal disease, or ESRD , according to the Centers for Disease Control and Prevention. The prevalence and incidence of CKD is increasing in all segments of the U.S. population.
CKD significantly impacts the United States, or U.S. , healthcare system, potentially affecting approximately 37 million patients and costing Medicare nearly $125 billion annually for treating Medicare beneficiaries with CKD or end-stage renal disease, or ESRD , according to the Centers for Disease Control and Prevention. Our two commercial products address certain complications of kidney disease.
The progression of CKD towards renal failure is complicated by multiple conditions which further deteriorate kidney function and the general health of patients if left untreated. Typically the prevalence of these conditions increases as CKD progresses. For instance, patients with CKD often experience high phosphorus and develop hyperphosphatemia, which can result in bone disease, vascular calcification and calciphylaxis (skin ulceration).
The progression of CKD towards renal failure is complicated by multiple conditions which further deteriorate kidney function and the general health of patients if left untreated. Typically, the prevalence of these conditions increases as CKD progresses.
Stabilization of HIF by prolyl hydroxylase inhibition leads to the release of erythropoietin, a shift to anaerobic metabolism (glycolysis) and decreased inflammatory responses that collectively lessen kidney ischemia-reperfusion injury and ameliorate the decline in kidney function. Data from our preclinical studies showed AKB-9090 to be highly active in lessening the severity of AKI in an animal model of ischemia-reperfusion injury.
Stabilization of HIF by prolyl hydroxylase inhibition leads to the release of erythropoietin, a shift to anaerobic metabolism (glycolysis) and decreased inflammatory responses that collectively lessen kidney ischemia-reperfusion injury and ameliorate the decline in kidney function seen in many clinical settings including CS-AKI.
Cyclerion Therapeutics License Agreement In June 2021, we entered into the Cyclerion Agreement with Cyclerion Therapeutics, Inc., or Cyclerion , under which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase, or sGC , stimulator.
In June 2021, we acquired from Cyclerion Therapeutics, Inc., or Cyclerion , an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase, or sGC , stimulator. We believe there is potential to explore the use of praliciguat for indications within kidney disease.
This is particularly true of medications covered under the ESRD Prospective Payment System, or PPS , in Medicare, or the ESRD Bundle , a payment structure with a flat base rate per dialysis session adjusted for individual patient and facility characteristics.
Medications covered under the ESRD Prospective Payment System, or PPS , in Medicare are known as the ESRD Bundle, a payment structure with a flat base rate per dialysis session adjusted for individual patient and facility characteristics. Dialysis-related drugs are included in the ESRD Bundle if they fall into functional categories such as anemia management.
We plan to mitigate potential commercial supply risks for vadadustat, if any, through inventory management and we may enter into additional manufacturing arrangements for both drug substance and drug product if vadadustat is approved in the U.S. Vadadustat is a small molecule.
In addition, we and Esteve Química, S.A. have agreed to negotiate the terms of a new supply agreement for the manufacture of Vafseo drug substance for commercial use. We plan to mitigate potential commercial supply risks for Vafseo, if any, through inventory management and we may enter into additional manufacturing arrangements for both drug substance and drug product.
Market Opportunity – Hyperphosphatemia and Iron Deficiency Anemia Hyperphosphatemia is a metabolic disorder characterized by elevated serum phosphorus levels. Phosphorus is a vital element required for most cellular processes and, in individuals with normal kidney function, excess dietary phosphorus is removed by the kidneys and excreted in urine.
Phosphorus is a vital element required for most cellular processes and, in individuals with normal kidney function, excess dietary phosphorus is removed by the kidneys and excreted in urine. In adults with functioning kidneys, normal serum phosphorus levels are 2.5 to 4.5 mg/dL.
The TDAPA provides separate payment for eligible new drugs for two years based on the drug’s Average Sales Price, or ASP , that will be in addition to the base rate in order to facilitate the adoption of innovative therapies.
The TDAPA provides separate payment for new drugs for two years based on the drug’s Average Sales Price that is in addition to the base rate in the bundle in order to facilitate the adoption of innovative therapies. Vafseo met the criteria for TDAPA in the anemia management ESRD PPS functional category beginning on January 1, 2025.
All clinical and commercial supplies are manufactured under current Good Manufacturing Practices, or cGMPs , which is a regulatory standard for the production of pharmaceuticals that will be used in humans. Vadadustat We currently rely on a single-source supplier for the direct manufacture of our drug substance and drug product for clinical and commercial supply of vadadustat.
Both of these occurrences would be beyond our control. All clinical and commercial supplies are manufactured under current Good Manufacturing Practices, or cGMPs , which is a regulatory requirement for the production of pharmaceuticals that will be used in humans.
We continue to explore additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics through both internal research and external innovation to leverage our fully integrated team. Strategy Our strategic focus and business operations are driven by our commitment to patients.
We continue to explore additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics through both internal research and external innovation to leverage our fully integrated team. Strategy Our deep understanding of kidney disease helps us serve the unmet needs of kidney patients and others impacted by chronic and debilitating illness.
KG, or Medice , pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in patients with CKD in the EEA , the UK, Switzerland and Australia, or the Medice Territory . • In Japan, vadadustat is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent patients under the trade name Vafseo, and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporation, or MTPC .
In Japan, Vafseo is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent patients and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporation, or MTPC .
In Taiwan, vadadustat is approved for the treatment of symptomatic anemia due to CKD in adult patients on chronic maintenance dialysis and in Korea as an anemia treatment for patients with CKD on hemodialysis. MTPC plans to commercialize vadadustat in Taiwan. We continue to pursue approval for vadadustat in the U.S.
In Taiwan, Vafseo is approved for the treatment of symptomatic anemia due to CKD in adult patients on chronic maintenance dialysis and was launched in October 2024 by Tai Tien Pharmaceutical Company, an affiliate of MTPC. In Korea, Vafseo is approved as an anemia treatment for patients with CKD on hemodialysis.
The discovery of HIF laid the foundation to explore the central role of oxygen sensing in many diseases. As we have seen through the development of vadadustat as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adaptive, protective responses during hypoxic or ischemic conditions.
As we have Akebia Therapeutics, Inc. | Form 10-K | Page 6 Table of Contents seen through the development of Vafseo as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adaptive, protective responses during hypoxic or ischemic conditions.
We have established relationships with several CMOs and expect to continue to rely on either existing or alternative distributors and CMOs to distribute our products and supply our ongoing and planned preclinical studies and clinical trials and for commercial production.
We have established relationships with several CMOs and expect to continue to rely on either existing or alternative CMOs and distributors to manufacture or distribute our products to support ongoing and planned preclinical, clinical and commercial distribution activities. Our CMOs have other clients and may have other priorities that could affect manufacturing line capacity and/or delivery schedules.
In addition, in 2020 approximately 44% of patients treated with a phosphate binder were treated solely with a calcium-based binder, which can lead to side effects such as increased cardiovascular risk, hypercalcemia and gastrointestinal-related Akebia Therapeutics, Inc. | Form 10-K | Page 9 Table of Content s adverse events.
In addition, in 2020 approximately 44% of patients treated with a phosphate binder were treated solely with a calcium-based binder, which can lead to side effects such as increased cardiovascular risk, hypercalcemia and gastrointestinal-related adverse events. Due to the risks associated with calcium-based binders, in 2017 Kidney Disease: Improving Global Outcomes, recommended that clinicians limit the use of calcium-based binders.
Serious TEAEs were lower in vadadustat treated patients at 49.7% compared to 56.5% for darbepoetin alfa treated patients. The incidence of TEAEs during the Conversion study in the vadadustat treated patients was 88.3%, and 89.3% in darbepoetin alfa treated patients.
The incidence of TEAEs during the Conversion study in vadadustat treated patients was 89.1% and 87.7% in darbepoetin alfa-treated patients.
The most commonly reported TEAEs in patients treated with vadadustat QD, vadadustat TIW, and darbepoetin alfa were COVID-19 (13.3%, 12.5%, and 13.0% respectively), diarrhea (13.3%, 14.4%, and 5.6% respectively), and anemia (7.6%, 10.6%, and 9.3% respectively). Pipeline We continue to add to our pipeline and portfolio of novel therapeutics through internal research, discovery and development.
The most commonly reported TEAEs in patients treated with vadadustat QD, vadadustat TIW, and darbepoetin alfa were COVID-19 (13.3%, 12.5%, and 13.0% respectively), diarrhea (13.3%, 14.4%, and 5.6% respectively), and anemia (7.6%, 10.6%, and 9.3% respectively). Manufacturing and Supply Overview We neither own nor operate, and currently have no plans to own or operate, any manufacturing or distribution facilities.
Akebia Therapeutics, Inc. | Form 10-K | Page 7 Table of Content s • In the European Union, or EU , the UK, Switzerland and Australia, vadadustat is approved under the trade name Vafseo for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis.
In the European Union, or EU , the United Kingdom, or UK , Switzerland and Australia, Vafseo is approved for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis. Our partner MEDICE Arzneimittel Pütter GmbH & Co.
Similarly, each starting dose regimen of vadadustat and the combined vadadustat-treated Akebia Therapeutics, Inc. | Form 10-K | Page 14 Table of Content s group achieved the secondary efficacy endpoint of the mean change in Hb between baseline and the secondary evaluation period (weeks 46-52).
Similarly, each starting dose regimen of vadadustat and the combined vadadustat-treated group achieved the secondary efficacy endpoint of the mean change in Hb between baseline and the secondary evaluation period (weeks 46-52). In the FO 2 CUS study in hemodialysis patients (n=456): • Primary Efficacy Endpoint Results : Vadadustat demonstrated non-inferiority to Mircera.
Ferric citrate hydrate, which launched in May 2014 and is being marketed in Japan by Torii under the brand name Riona, is indicated as an oral treatment for the improvement of hyperphosphatemia in patients with CKD, including NDD-CKD and DD-CKD.
Ferric citrate hydrate has also been approved in Japan, and is marketed and sold by our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceutical Co., Ltd., collectively, JT and Torii , as an oral treatment for the improvement of hyperphosphatemia in patients with CKD, including DD-CKD and NDD-CKD, and for the treatment of adult patients with IDA under the trade name Riona in Japan.
Vadadustat Market Opportunity Anemia is common in patients with CKD, and its prevalence increases with disease progression. Anemia due to CKD results from inadequate EPO levels, negatively affecting RBC production. Left untreated, anemia accelerates the overall deterioration of patient health with increased morbidity and mortality.
Drive Vafseo to be Standard of Care in the Treatment of Anemia due to CKD Anemia is common in patients with CKD, and its prevalence increases with disease progression. Anemia due to CKD results from inadequate erythropoietin, or EPO , levels, negatively affecting red blood cell production.
If there are too few RBCs or if hemoglobin levels are low, the cells in the body will not get enough oxygen. IDA is a common form of anemia that is caused by patients not having enough iron to manufacture healthy RBCs. Although anyone can develop IDA, IDA is particularly common in NDD-CKD patients.
IDA is a common form of anemia that is caused by patients not having enough iron to manufacture healthy RBCs. Although anyone can develop IDA, it is particularly common in NDD-CKD patients. IDA is associated with fatigue, lethargy, decrease quality of life, cardiovascular complications, hospitalizations and increased mortality.
Auryxia has contributed consistent, meaningful revenue to the business since it became part of our portfolio in 2018.
Today, we market Auryxia in the U.S. Auryxia became part of our portfolio in 2018 and has historically contributed meaningful revenue to the business. In March 2025, Auryxia will lose exclusivity, or LoE .
In September 2023, we completed our resubmission to our New Drug Application, or NDA , for the treatment of anemia due to CKD in adult patients on dialysis to the U.S. Food and Drug Administration, or FDA .
Our current portfolio includes: Vafseo was approved by the U.S. Food and Drug Administration, or the FDA , in March 2024 for the treatment of anemia due to CKD in adult patients on dialysis for at least three months. Shipment of Vafseo commenced in January 2025.
Based on the data and our strategic business considerations, we may not pursue vadadustat as a treatment for ARDS. Retinopathy of Prematurity (ROP) ROP is the leading cause of blindness in preterm infants globally and occurs due to incomplete retinal development and abnormal blood vessel growth in the retina.
In earlier studies, vadadustat lessened the severity of COVID-19 pneumonia in a clinical trial (NCT04478071) and improved outcomes in animal models of acute lung injury. Retinopathy of Prematurity (ROP) ROP is the leading cause of blindness in preterm infants globally and occurs due to incomplete retinal development and abnormal blood vessel growth in the retina.
Through pipeline advancement, our goal is to target new market opportunities in areas of high unmet need. • Explore Strategic Growth: We continue to explore additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics through both internal research and external innovation to leverage our fully integrated team.
We continue to explore strategic growth, which includes additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics, through external innovation to leverage our fully integrated team. We plan to make strategic use of capital and will also continue our approach of financial discipline, cross-organizational efficiency and operational effectiveness.
Acute Kidney Injury (AKI) AKI is a sudden decline in the ability of the kidneys to work and perform their normal functions. AKI occurs in 20-30% of the approximately two million patients that undergo cardiac surgeries annually and there are no current treatments available for cardiovascular surgery-related AKI.
We intend to explore AKB-9090 for potential use in CS-AKI and ARDS, and AKB-10108 for potential use in ROP. Cardiac Surgery-related Acute Kidney Injury AKI is a sudden decline in the ability of the kidneys to work and perform their normal functions.
We believe there are compelling data supporting a positive benefit-risk profile for the use of vadadustat broadly in patients with CKD.
The FDA expressed safety concerns, noting failure to meet non-inferiority in Major Adverse Cardiovascular Events, or MACE , in the non-dialysis patient population. While we have since secured FDA approval for use in dialysis patients, we believe there are compelling data supporting a positive benefit-risk profile for the use of Vafseo broadly in patients with CKD.
Background on Chronic Kidney Disease There is a clear need to improve the quality of life outcomes for people living with kidney disease. CKD is a condition in which the kidneys are progressively damaged to the point that they cannot properly filter the blood circulating in the body.
We have established the company as a leader in the kidney community, and we believe our cross-organizational expertise in renal disease positions us for success. Chronic kidney disease, or CKD , is a condition in which the kidneys are progressively damaged to the point that they cannot properly filter the blood circulating in the body.
We believe there is a significant opportunity for vadadustat to address limitations of injectable ESAs and become a new oral option for the treatment of anemia due to CKD in adult patients on dialysis, if approved.
We believe there is a significant opportunity for Vafseo to become the standard of care for the treatment of anemia due to CKD for adult patients on dialysis and, if approved, not on dialysis. Akebia Therapeutics, Inc. | Form 10-K | Page 7 Table of Contents Vafseo is an oral HIF-PH inhibitor that stimulates the body's natural response to hypoxia.
If we obtain FDA approval for vadadustat for the treatment of anemia due to CKD in adult patients, we plan to commercialize vadadustat in the U.S. with CSL Vifor. Today, we have an established and embedded commercial team with approximately 30 key account managers supported by our commercial operations team.
Today, we have an established and embedded commercial team with approximately 35 key account managers, or KAMs , supported by our commercial operations team. Upon Vafseo's U.S. approval and in parallel with contracting and protocol development, our KAMs began detailing Vafseo to prescribers.
While injectable ESAs can be effective in raising hemoglobin levels, they have the potential to cause significant side Akebia Therapeutics, Inc. | Form 10-K | Page 10 Table of Content s effects, and need to be injected subcutaneously or intravenously. In particular, injectable ESAs may lead to thrombosis, stroke, myocardial infarction and death.
While injectable ESAs can be effective in raising hemoglobin levels, they have the potential to cause significant side effects and need to be injected subcutaneously or intravenously. The current market opportunity for the treatment of anemia due to CKD in adult patients on dialysis is approximately $1 billion in the U.S. based on current ESA pricing.
IDA is associated with fatigue, lethargy, decrease quality of life, cardiovascular complications, hospitalizations and increased mortality. We estimate that there are more than 500,000 adult patients in the U.S. with NDD-CKD diagnosed with IDA and managed by a nephrologist.
Akebia Therapeutics, Inc. | Form 10-K | Page 9 Table of Contents We estimate that there are more than 500,000 adult patients in the U.S. with NDD-CKD diagnosed with IDA and managed by a nephrologist. Currently, there are two forms of iron therapy used to treat IDA: oral iron supplements and iron delivered via intravenous infusion, or IV .
The information on our website is not part of this Annual Report on Form 10-K. Akebia Therapeutics, Inc. | Form 10-K | Page 49 Table of Content s
For more information about our manufacturing agreements for Vafseo, see Part II, Akebia Therapeutics, Inc. | Form 10-K | Page 14 Table of Contents
We have invested resources to build out a preclinical portfolio and have selected two candidates for further preclinical development: AKB-9090, a drug targeting critical-care indications, and AKB-10108, a drug targeting conditions related to premature birth. We intend to explore AKB-9090 for potential use in AKI and ARDS, and AKB-10108 for potential use in ROP.
We also leverage our research and development competency and expertise in HIF-based technology to both build on our commitment to kidney disease and also address areas of unmet medical need outside of kidney disease. We have invested resources to build out a preclinical portfolio and have selected two candidates for further preclinical development: AKB-9090 and AKB-10108.
We currently rely on a single-source supplier for the manufacture of our drug substance for clinical and commercial supply of Auryxia. The drug substance for Auryxia is supplied by Siegfried Evionnaz SA, pursuant to a supply agreement, as amended, with pricing structured on a per-kilogram ba sis.
Vafseo We currently rely on suppliers for the direct manufacture of our drug substance and drug product for clinical and commercial supply of Vafseo.
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Our purpose is to better the life of each person impacted by kidney disease, and we have established ourselves as a leader in the kidney community. We believe our demonstrated ability to deliver value broadly to the kidney community has enabled us to build a sustainable company.
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Our team has significant expertise in hypoxia-inducible factor, or HIF , science having developed and commercialized Vafseo® (vadadustat), an oral HIF prolyl hydroxylase, or HIF-PH , inhibitor and have selected two additional HIF-based molecules for preclinical development.
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Upon this solid foundation and our continued commitment to patients, we believe focusing on all patients who can realize a meaningful benefit from our medicines will deliver value for our shareholders.
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We have commercial supply agreements for the purchase of Vafseo in place with dialysis organizations caring for nearly 100% of dialysis patients in the U.S.
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Our current portfolio and hypoxia-inducible factor (HIF)-based pipeline includes: Product Indication Region(s) Discovery Phase 1 Phase 2 Phase 3 Regulatory Review Commercial Approval In Market Auryxia® (ferric citrate) Hyperphosphatemia, IDA United States 1 , Japan 2 and Taiwan 2 Vafseo® Anemia DD-CKD, Anemia NDD-CKD Japan 3 Vafseo® Anemia DD-CKD European Union 4 , United Kingdom 4 , Switzerland 4 , Australia 4 , Taiwan 5 and Korea 5 Vadadustat Anemia DD-CKD United States 1 Vadadustat Anemia NDD-CKD Global 6 AKB-9090 AKI, ARDS Global 1 AKB-10108 ROP Global 1 1 Marketed by Akebia 2 Marketed by JT Torii 3 Marketed by MTPC 4 To be marketed by Medice 5 To be marketed by MTPC 6 To be marketed by Akebia; MTPC and Medice have certain rights in their territories Auryxia® (ferric citrate) is an orally administered medicine approved and marketed in the United States, or U.S. , for two indications: (1) the control of serum phosphorus levels in adult patients with dialysis dependent chronic kidney disease, or DD-CKD , and (2) the treatment of iron deficiency anemia, or IDA , in adult patients with non-dialysis-dependent chronic kidney disease, or NDD-CKD .
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The current U.S. market opportunity for the treatment of anemia due to CKD in patients with dialysis is approximately $1 billion based on current erythropoiesis-stimulating agent, or ESA , pricing, and Vafseo is the only oral HIF-based treatment available in the U.S.
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Today, we market Auryxia in the U.S. with our well-established, nephrology-focused commercial organization. Our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceutical Co., Ltd., collectively, JT and Torii , commercialize ferric citrate hydrate as Riona in Japan.
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KG, or Medice , has an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in defined territories and launched Vafseo in Germany, Austria, Switzerland, the Netherlands and certain other countries in Europe in 2024.
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Vafseo ® (vadadustat) is a HIF prolyl hydroxylase, or HIF-PH , inhibitor, approved in 36 countries as a treatment for anemia due to chronic kidney disease, or CKD .
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We believe the dynamics of Auryxia reimbursement being included in the ESRD bundle under Medicare Part B could result in slower revenue decline after the LoE date than in other LoE situations, but the impact of LoE on future Auryxia revenues will depend on many factors, including our ability to maintain contracts with dialysis organizations, the timing and number of generics and the pricing of generics and other products on the market that compete with Auryxia.
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In May 2023, we entered into a License Agreement with MEDICE Arzneimittel Pütter GmbH & Co.
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Our HIF-based product candidates and other pipeline assets are being evaluated to target areas of unmet needs. The discovery of HIF laid the foundation to explore the central role of oxygen sensing in many diseases.
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In October 2023, the FDA acknowledged that the resubmission was complete, classified it as a Class 2 response and set a user fee goal date, or PDUFA Date , of March 27, 2024. We initially submitted an NDA to the FDA for vadadustat in March of 2021.
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Our commitment to patients informs our business decisions and short and long-term planning. There is a clear need to improve quality of life outcomes for people living with kidney disease. The prevalence and incidence of CKD is increasing in the U.S. population.
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The FDA expressed safety concerns, noting failure to meet non-inferiority in Major Adverse Cardiovascular Events, or MACE , in the non-dialysis patient population, the increased risk of thromboembolic events driven by vascular access thrombosis in dialysis patients and the risk of drug-induced liver injury.
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With two revenue-generating products and the research and development capabilities to discover, advance and commercialize new therapies, our intention is to both fulfill our purpose to better the lives of those impacted by kidney disease as well as leverage our internally developed innovations and explore therapies in other disease areas with high unmet needs. Our strategic imperatives are threefold: 1.
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In October 2022, we submitted a Formal Dispute Resolution Request, or FDRR , with the FDA regarding the CRL focused on the favorable balance of the benefits and risks of vadadustat for the treatment of adult patients with anemia due to CKD on dialysis.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

410 edited+154 added−111 removed422 unchanged
Biggest changeOur ability to generate product revenue and achieve profitability depends on our ability to manage expenses and the overall success of Auryxia, vadadustat, if approved, and any current or future product candidates, including those that may be in-licensed or acquired, which depends on several factors, including: • our ability to obtain approval for vadadustat in the U.S. in a timely manner or at all; • obtaining adequate or favorable pricing and reimbursement from private and governmental payors for Auryxia, vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired; • obtaining and maintaining market acceptance of Auryxia, vadadustat, if approved, and any other product candidate, including those that may be in-licensed or acquired; • the size of any market in which Auryxia, vadadustat and any other product or product candidate, including those that may be in-licensed or acquired, receives approval and obtaining adequate market share in those markets; • the timing and scope of marketing approvals for vadadustat, if approved, and any other product candidate, if approved, including those that may be in-licensed or acquired; • maintaining marketing approvals for Auryxia, vadadustat, if approved, and any other product, including those that may be in-licensed or acquired; Akebia Therapeutics, Inc. | Form 10-K | Page 50 Table of Content s • actual or perceived advantages or disadvantages of our products or product candidates as compared to alternative treatments, including their respective safety, tolerability and efficacy profiles, the potential convenience and ease of administration and cost; • maintaining an acceptable safety and tolerability profile of our approved products, including the frequency and severity of any side effects; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, based, in part, on their perception of our clinical trial data and/or the actual or perceived safety, tolerability and efficacy profile; • establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate supplies of products that are compliant with good manufacturing practices, or GMPs , to support the clinical development and the market demand for Auryxia, vadadustat, if approved, and any other product and product candidate, including those that may be in-licensed or acquired; • current and future restrictions or limitations on our approved or future indications and patient populations or other adverse regulatory actions or in the event that the FDA requires Risk Evaluation and Mitigation Strategies, or REMS , or risk management plans that use restrictive risk minimization strategies; • the effectiveness of our collaborators' and our sales, marketing, manufacturing and distribution strategies and operations; • competing effectively with any products for the same or similar indications as our products; • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents and trade secrets; and • the adverse impact of the recent COVID-19 pandemic on CKD patients and the phosphate binder market in which we compete.
Biggest changeOur ability to generate product revenue and achieve profitability depends on our ability to manage expenses and the overall success of Auryxia, Vafseo and any current or future product candidates, including those that may be in-licensed or acquired, which depends on several factors, including: • obtaining adequate or favorable pricing and reimbursement from private and governmental payors for Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired; • obtaining and maintaining market acceptance of Auryxia, Vafseo and any other product candidate, including those that may be in-licensed or acquired; • the size of any market in which Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired, receives approval and obtaining adequate market share in those markets; • maintaining marketing approvals for Auryxia, Vafseo and any other product, including those that may be in-licensed or acquired; • obtaining regulatory approval for any label expansion for Vafseo, including the timing and scope thereof; • our ability to maintain contracts with dialysis organizations for the sale of Auryxia and Vafseo in the U.S.; • actual or perceived advantages or disadvantages of our products or product candidates as compared to alternative treatments, including their respective safety, tolerability and efficacy profiles, the potential convenience and ease of administration and cost; • maintaining an acceptable safety and tolerability profile of our approved products, including the frequency and severity of any side effects; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, based, in part, on their perception of our clinical trial data and/or the actual or perceived safety, tolerability and efficacy profile; Akebia Therapeutics, Inc. | Form 10-K | Page 49 Table of Contents • the timing and scope of marketing approvals for any product candidate, if approved, including those that may be in-licensed or acquired; • establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate supplies of products that are compliant with good manufacturing practices, or GMPs , to support the clinical development and the market demand for Auryxia, Vafseo and any other product and product candidate, including those that may be in-licensed or acquired; • the potential impact of geopolitical pressures or the BIOSECURE Act on our ability to conduct our business as currently conducted; • current and future restrictions or limitations on our approved or future indications and patient populations or other adverse regulatory actions or in the event that the FDA requires Risk Evaluation and Mitigation Strategies, or REMS , or risk management plans that use restrictive risk minimization strategies; • the effectiveness of our collaborators' and our sales, marketing, manufacturing and distribution strategies and operations; • competing effectively with any products for the same or similar indications as our products (including generics); • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents and trade secrets; and • the adverse impact of the COVID-19 pandemic on CKD patients and the phosphate binder market in which we compete.
Identifying and qualifying patients to participate in clinical trials is critical to our success. The timing of our clinical trials depends, in part, on the speed at which we can recruit patients to participate in our clinical trials.
Identifying and qualifying patients to participate in clinical trials is critical to the success of our clinical trials. The timing of our clinical trials depends, in part, on the speed at which we can recruit patients to participate in our clinical trials.
Obtaining marketing approval in the U.S. and other jurisdictions for any product candidate depends upon numerous factors, many of which are subject to the substantial discretion of the regulatory authorities, including that regulatory agencies may not complete their review processes in a timely manner and, following completion of the review process, may not grant marketing approval or such marketing approval may be limited.
Obtaining marketing approval in the U.S. and other jurisdictions for any product candidate depends upon numerous factors, many of which are subject to the substantial discretion of the regulatory authorities, including that regulatory agencies may not complete their review processes in a timely manner and/or, following completion of the review process, may not grant marketing approval or such marketing approval may be limited.
Marketing approvals may be subject to limitations on the approved indicated uses for which the product may be marketed or other conditions of approval, or contain requirements or commitments for potentially costly post-marketing studies and surveillance to monitor the safety and efficacy of the product, including REMS, or registries or observational studies.
Marketing approvals may be subject to limitations on the approved indicated uses for which the product may be marketed, other conditions of approval, or contain requirements or commitments for potentially costly post-marketing studies and surveillance to monitor the safety and efficacy of the product, including REMS, or registries or observational studies.
Health Insurance Portability and Accountability Act of 1996, or HIPAA , as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH , state privacy and data protection laws, such as the California Consumer Privacy Act, or CCPA , as amended by the California Privacy Rights Act of 2020, or CPRA , as well as other state consumer protection laws, GDPR, any additional applicable EU member state, or EU Member State , data protection laws in force from time to time, the retained EU law version of the General Data Protection Regulation as saved into United Kingdom law by virtue of section 3 of the United Kingdom's European Union (Withdrawal) Act 2018, or the EU GDPR ; • federal and state laws requiring the submission of accurate product prices and notifications of price increases; • federal and state securities laws; • environmental, health and safety laws and regulations; and • international trade laws, which are laws that regulate the sale, purchase, import, export, re-export, transfer and shipment of goods, products, materials, services and technology.
Health Insurance Portability and Accountability Act of 1996, or HIPAA , as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH , state privacy and data protection laws, such as the California Consumer Privacy Act, or CCPA , as amended by the California Privacy Rights Act of 2020, or CPRA , as well as other state consumer protection laws, GDPR, any additional applicable EU member state, or EU Member State , data protection laws in force from time to time, the retained EU law version of the General Data Protection Regulation as saved into United Kingdom law by virtue of section 3 of the United Kingdom's European Union (Withdrawal) Act 2018; • federal and state laws requiring the submission of accurate product prices and notifications of price increases; • federal and state securities laws; • environmental, health and safety laws and regulations; and • international trade laws, which are laws that regulate the sale, purchase, import, export, re-export, transfer and shipment of goods, products, materials, services and technology.
Following the withdrawal of the UK from the EU, the UK Data Protection Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligations to those set forth by GDPR.
Following the withdrawal of the UK from the EU, the UK Data Protection Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligations to those set forth by GDPR.
Each warrant is exercisable for eight years from date of issuance. If any or all of the warrants are exercised, our stockholders could realize dilution, and the value of their shares could decrease.
Each warrant is exercisable for eight years from the date of issuance. If any or all of the warrants are exercised, our stockholders could realize dilution, and the value of their shares could decrease.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare may adversely affect: • the demand for Auryxia and any products candidates for which we receive marketing approval; • our ability to set a price that we believe is fair for our products; • our ability to obtain and maintain coverage and reimbursement approval for Auryxia or any other approved product; • our ability to generate revenues and achieve or maintain profitability; and • the level of taxes that we are required to pay.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare may adversely affect: • the demand for Auryxia, Vafseo and any product candidates for which we receive marketing approval; • our ability to set a price that we believe is fair for our products; • our ability to obtain and maintain coverage and reimbursement approval for Auryxia, Vafseo or any other approved product; • our ability to generate revenues and achieve or maintain profitability; and • the level of taxes that we are required to pay.
Conditions that could indicate impairment and necessitate such a review include, but are not limited to, Auryxia’s commercial performance, our inability to execute on our strategic initiatives, the deterioration of our market capitalization such that it is significantly below our net book value, a significant adverse change in legal factors, unexpected adverse business conditions, and an adverse action or assessment by a regulator.
Conditions that could indicate impairment and necessitate such a review include, but are not limited to, Auryxia’s and Vafseo's commercial performance, our inability to execute on our strategic initiatives, the deterioration of our market capitalization such that it is significantly below our net book value, a significant adverse change in legal factors, unexpected adverse business conditions, and an adverse action or assessment by a regulator.
These restrictions include, but are not limited to, the following: • the Food, Drug and Cosmetic Act of 1938, as amended, or FDCA , which among other things, strictly regulates drug product marketing and promotion and prohibits manufacturers from marketing such products for off-label use; • federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs, and laws requiring notification of price increases; • the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; • the federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties, and violations of the FDCA, the federal government pricing laws, and the federal Anti-Kickback Statute trigger liability under the federal False Claims Act; • HIPAA, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; Akebia Therapeutics, Inc. | Form 10-K | Page 75 Table of Content s • HIPAA, as amended by the HITECH, and their respective implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • the federal Open Payments Act (the former Physician Payments Sunshine Act) requires applicable manufacturers of covered drugs to report payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and gift ban and transparency statutes, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by state Medicaid or other programs, or non-governmental third party payors, including private insurers, and which are not preempted by federal laws and often differ from state to state, thus complicating compliance efforts; and • U.S. state laws restricting interactions with healthcare providers and other members of the healthcare community or requiring pharmaceutical manufacturers to implement certain compliance standards, which vary from state to state.
These restrictions include, but are not limited to, the following: • the Food, Drug and Cosmetic Act of 1938, as amended, or FDCA , which among other things, strictly regulates drug product marketing and promotion and prohibits manufacturers from marketing such products for off-label use; Akebia Therapeutics, Inc. | Form 10-K | Page 74 Table of Contents • federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs, and laws requiring notification of price increases; • the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; • the federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties, and violations of the FDCA, the federal government pricing laws, and the federal Anti-Kickback Statute trigger liability under the federal False Claims Act; • HIPAA, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; • HIPAA, as amended by the HITECH, and their respective implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • the federal Open Payments Act (the former Physician Payments Sunshine Act) requires applicable manufacturers of covered drugs to report payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • analogous state laws and regulations, such as state anti-kickback and false claims laws and gift ban and transparency statutes, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by state Medicaid or other programs, or non-governmental third party payors, including private insurers, and which are not preempted by federal laws and often differ from state to state, thus complicating compliance efforts; and • U.S. state laws restricting interactions with healthcare providers and other members of the healthcare community or requiring pharmaceutical manufacturers to implement certain compliance standards, which vary from state to state.
The exercise or vesting of any such options, restricted stock units, or other derivative securities, and the subsequent sale of the underlying common stock, could cause a further decline in our stock price. These sales also might make it difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
The exercise or vesting of any such options, restricted stock units, or other securities, and the subsequent sale of the underlying common stock, could cause a further decline in our stock price. These sales also might make it difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
If coverage and reimbursement terms change, MTPC may not be able to, or may decide not to, continue commercialization of Vafseo in Japan. Furthermore, vadadustat was approved in Europe and Australia for the treatment of anemia due to CKD in DD-CKD patients. In Europe, reimbursement is obtained on a country-by-country basis and it is a time consuming process.
If coverage and reimbursement terms change, MTPC may not be able to, or may decide not to, continue commercialization of Vafseo in Japan. Furthermore, Vafseo was approved in Europe and Australia for the treatment of anemia due to CKD in DD-CKD patients. In Europe, reimbursement is obtained on a country-by-country basis and it is a time consuming process.
Within Medicare, for oral drugs dispensed by pharmacies and also administered in facilities, coverage and reimbursement may vary depending on the setting. CMS, local Medicare administrative contractors, Medicare Part D plans and/or PBMs operating on behalf of Medicare Part D plans, may have some responsibility for determining the medical necessity of such drugs, and therefore coverage, for different patients.
Within Medicare, for oral drugs dispensed by pharmacies and also administered in facilities, coverage and reimbursement may vary depending on the setting. CMS, local Medicare administrative contractors, Medicare Advantage and/or Part D plans and/or PBMs operating on behalf of such plans, may have some responsibility for determining the medical necessity of such drugs, and therefore coverage, for different patients.
For example, on June 4, 2021, we entered into a license agreement, the Cyclerion Agreement , with Cyclerion Therapeutics Inc., or Cyclerion , pursuant to which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase, or sGC , stimulator.
For example, on June 4, 2021, we entered into a license agreement, or the Cyclerion Agreement , with Cyclerion Therapeutics Inc., or Cyclerion , pursuant to which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase stimulator.
In addition, we may need to further adjust the size of our workforce as a result of changes to our expectations for our business, which can result in management being required to divert a disproportionate amount of its attention away from our day-to-day activities and devote a substantial amount of time to managing these growth-related activities and related expenses.
In addition, we may need to adjust the size of our workforce as a result of changes to our expectations for our business, which can result in management being required to divert a disproportionate amount of its attention away from our day-to-day activities and devote a substantial amount of time to managing these growth-related activities and related expenses.
As a result of these and other activities, we are or may become subject to additional risks in developing and commercializing Auryxia and vadadustat outside the U.S., including, among others: • political, regulatory, compliance and economic developments, weakness or instability that could restrict our ability to manufacture, market and sell our products; • changes in international medical reimbursement policies and programs; • changes in healthcare policies of foreign jurisdictions; • trade protection measures, including import or export licensing requirements and tariffs and our compliance therewith; • our ability to develop or manage relationships with qualified local distributors and trading companies; • diminished protection of intellectual property in some countries outside of the U.S.; • differing labor regulations and business practices; • compliance with laws, including the U.S.
As a result of these and other activities, we are or may become subject to additional risks in developing and commercializing Auryxia and Vafseo outside the U.S., including, among others: • political, regulatory, compliance and economic developments, weakness or instability that could restrict our ability to manufacture, market and sell our products; • changes in international medical reimbursement policies and programs; • changes in healthcare policies of foreign jurisdictions; • trade protection measures, including import or export licensing requirements and tariffs and our compliance therewith; • our ability to develop or manage relationships with qualified local distributors and trading companies; • diminished protection of intellectual property in some countries outside of the U.S.; • differing labor regulations and business practices; • compliance with laws, including the U.S.
Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S. However, some privacy advocacy groups have already challenged or suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S.
Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S. However, some privacy advocacy groups have challenged or suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S.
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for Auryxia and any product candidates for which we receive marketing approval or additional pricing pressures.
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for Auryxia or Vafseo and any product candidates for which we receive marketing approval or additional pricing pressures.
In addition, our net product revenue requires judgement and includes estimates for rebates and product returns, which can fluctuate from quarter-to-quarter and year-over-year. If our net product revenue is lower than anticipated, including as a result of higher expenses, our business could be harmed.
In addition, our net product revenue requires judgement and includes estimates for rebates and product returns, which can fluctuate from quarter-to-quarter and year-over-year. If our net product revenue is lower than anticipated, including as a result of higher expenses or product returns, our business could be harmed.
Sales of substantial amounts of shares of our common stock or other securities by our employees or our other stockholders or by us under any shelf registration statement, pursuant to at-the-market offerings or otherwise, could dilute our stockholders, lower the market price of our common stock and impair our ability to raise capital through the sale of equity securities.
Sales of substantial amounts of shares of our common stock or other securities by our employees or our other stockholders or by us under our shelf registration statement, pursuant to at-the-market offerings or otherwise, could dilute our stockholders, lower the market price of our common stock and impair our ability to raise capital through the sale of equity securities.
Moreover, issues that may arise in any scale-up and technology transfer and continued commercial scale manufacture of our products may lead to significant delays in our development, marketing approval and commercial timelines for new products or affect commercial supply of Auryxia and negatively impact our financial performance.
Moreover, issues that may arise in any scale-up and technology transfer and continued commercial scale manufacture of our products may lead to significant delays in our development, marketing approval and commercial timelines for new products or affect commercial supply of Auryxia or Vafseo and negatively impact our financial performance.
In particular, we rely on CROs and other third parties to store and manage information from our clinical trials. We also rely on third parties to manage patient information for Auryxia. Additionally, the use of artificial intelligence based software is increasingly being used in the biopharmaceutical industry.
In particular, we rely on CROs and other third parties to store and manage information from our clinical trials. We also rely on third parties to manage patient information for Auryxia and Vafseo. Additionally, the use of artificial intelligence based software is increasingly being used in the biopharmaceutical industry.
In addition, under ASC 360, Property, Plant and Equipment , we are required to review our property and equipment and right-of-use assets whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable.
In addition, under ASC 360, Property, Plant and Equipment , we are required to review our property and equipment and right-of-use assets whenever events or changes in circumstances indicate that the carrying amount of an asset or asset group may not be recoverable.
Any of these events could significantly harm our business, financial condition and prospects. Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our product and product candidates on unfavorable terms to us.
Any of these events could significantly harm our business, financial condition and prospects. Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our products and product candidates on unfavorable terms to us.
We will incur significant liability if it is determined that we are promoting any “off-label” use of Auryxia or any other product we may develop, in-license or acquire or if it is determined that any of our activities violates the federal Anti-Kickback Statute.
We will incur significant liability if it is determined that we are promoting any “off-label” use of Auryxia, Vafseo or any other product we may develop, in-license or acquire or if it is determined that any of our activities violates the federal Anti-Kickback Statute.
Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D.
With respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D.
The new legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.
The legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.
Our reporting and payment obligations under the Medicaid Drug Rebate Program and other governmental drug pricing programs are complex and may involve subjective decisions. Any failure to properly comply with those obligations could subject us to penalties and sanctions.
Our reporting and payment obligations under the Medicaid Drug Rebate Program, Medicare and other governmental drug pricing programs are complex and may involve subjective decisions. Any failure to properly comply with those obligations could subject us to penalties and sanctions.
Our understanding of adverse events in prior clinical trials of our product candidates may change as we gather more information, the FDA may not agree with our assessment of adverse events and additional unexpected adverse events may be observed in future clinical trials or in the market.
Our understanding of adverse events in prior clinical trials of Vafseo or our product candidates may change as we gather more information, the FDA may not agree with our assessment of adverse events and additional unexpected adverse events may be observed in future clinical trials or in the market.
Our pending patent applications may not issue as patents and may not issue in all countries in which we develop, manufacture or potentially sell our product or in countries where others develop, manufacture and potentially sell products using our technologies. Moreover, our pending patent applications, if issued as patents, may not provide additional protection for our product.
Our pending patent applications may not issue as patents and may not issue in all countries in which we develop, manufacture or potentially sell our products or in countries where others develop, manufacture and potentially sell products using our technologies. Moreover, our pending patent applications, if issued as patents, may not provide additional protection for our products.
In February 2021, we entered into a royalty interest acquisition agreement, or the Royalty Agreement , with HealthCare Royalty Partners IV, L.P., or HCR , pursuant to which we sold to HCR our right to receive royalties and sales milestones for vadadustat, collectively the Royalty Interest Payments , in each case, payable to us under our Collaboration Agreement dated December 11, 2015, or the MTPC Agreement , with Mitsubishi Tanabe Pharma Corporation, or MTPC , subject to an annual maximum “cap” of $13.0 million, or the Annual Cap , and an aggregate maximum “cap” of $150.0 million, or the Aggregate Cap .
In February 2021, we entered into a royalty interest acquisition agreement, or the Royalty Agreement , with HealthCare Royalty Partners IV, L.P., or HCR , pursuant to which we sold to HCR our right to receive royalties and sales milestones for Vafseo, collectively the Royalty Interest Payments , in each case, payable to us under our Collaboration Agreement dated December 11, 2015, or the MTPC Agreement , with Mitsubishi Tanabe Pharma Corporation, or MTPC , subject to an annual maximum “cap” of $13.0 million, or the Annual Cap , and an aggregate maximum “cap” of $150.0 million, or the Aggregate Cap .
If we violate any consent order that we reach with the FTC, we may be subject to additional fines and compliance requirements. New laws also are being considered at both the state and federal levels.
If we violate any consent order that we reach with the FTC, we may be subject to additional fines and compliance requirements. Laws also are being considered at both the state and federal levels.
We have a significant number of shares that are subject to outstanding options and restricted stock units, and in the future we may issue additional options, restricted stock units, or other derivative securities convertible into our common stock.
We have a significant number of shares that are subject to outstanding options, restricted stock units and other securities convertible into our common stock, and in the future we may issue additional options, restricted stock units, or other securities convertible into our common stock.
While we are unable to quantify the impact of the recent COVID-19 pandemic on future revenues and revenue growth, the recent COVID-19 pandemic and the ongoing impacts from the recent COVID-19 pandemic continue to adversely and disproportionately impact CKD patients and the phosphate binder market.
While we are unable to quantify the impact of the COVID-19 pandemic on future revenues and revenue growth, the COVID-19 pandemic and the ongoing impacts from the COVID-19 pandemic continue to adversely and disproportionately impact CKD patients and the phosphate binder market.
Undesirable effects caused by, or other undesirable properties of, Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired, or competing commercial products or product candidates in development that utilize a common mechanism of action could cause us or regulatory authorities to interrupt, delay or halt clinical trials, could result in a more restrictive label or the delay, denial or withdrawal of marketing approval by the FDA or other regulatory authorities, and could lead to potential product liability claims.
Undesirable effects caused by, or other undesirable properties of, Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired, or competing commercial products or product candidates in development that utilize a common mechanism of action could cause us or regulatory authorities to interrupt, delay or halt clinical trials, could result in a more restrictive label or the delay, denial or withdrawal of marketing approval by the FDA or other regulatory authorities, and could lead to potential product liability claims.
In addition, any legal action against our licensor, licensees or us that seeks damages or an injunction of commercial activities relating to Auryxia, vadadustat or any other product candidates or other technologies, including those that may be in-licensed or acquired, could subject us to monetary liability, a temporary or permanent injunction preventing the development, marketing and sale of such products or such technologies, and/or require our licensor, licensees or us to obtain a license to continue to develop, market or sell such products or other technologies.
In addition, any legal action against our licensor, licensees or us that seeks damages or an injunction of commercial activities relating to Auryxia, Vafseo or any product candidates or other technologies, including those that may be in-licensed or acquired, could subject us to monetary liability, a temporary or permanent injunction preventing the development, marketing and sale of such products or such technologies, and/or require our licensor, licensees or us to obtain a license to continue to develop, market or sell such products or other technologies.
In October 2023, the FDA approved XPHOZAH® (tenapanor), a phosphate absorption inhibitor that is marketed by Ardelyx, Inc. and indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy, which may impact the market for Auryxia.
In October 2023, the FDA approved XPHOZAH® (tenapanor), a phosphate absorption inhibitor that is marketed by Ardelyx and indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy, which may adversely impact the market for Auryxia.
During the study, the most common TEAEs reported in vadadustat/darbepoetin alfa-treated patients were end-stage renal disease (34.7%/ 35.2%), hypertension (17.7%/ 22.1.%), hyperkalemia (12.3.%/ 15.6%), urinary tract infection (12.9%/ 12.0%), diarrhea (13.9%/ 10.0%), peripheral oedema (12.5%/ 10.5%), fall (9.6%/ 10%) and nausea (10%/ 8.2%). Serious TEAEs were 65.3% for vadadustat-treated patients and 64.5% for darbepoetin alfa-treated patients.
During the study, the most common TEAEs reported in Vafseo/darbepoetin alfa-treated patients were end-stage renal disease (34.7%/ 35.2%), hypertension (17.7%/ 22.1.%), hyperkalemia (12.3.%/ 15.6%), urinary tract infection (12.9%/ 12.0%), diarrhea (13.9%/ 10.0%), peripheral oedema (12.5%/ 10.5%), fall (9.6%/ 10%) and nausea (10%/ 8.2%). Serious TEAEs were 65.3% for Vafseo-treated patients and 64.5% for darbepoetin alfa-treated patients.
If they do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain or maintain marketing approval for Auryxia, vadadustat or any of our product candidates, and our business could be substantially harmed. We do not have the ability to independently conduct certain preclinical studies and clinical trials.
If they do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain or maintain marketing approval for Auryxia, Vafseo or any of our product candidates, and our business could be substantially harmed. We do not have the ability to independently conduct certain preclinical studies and clinical trials.
If we are not able to correct material weaknesses or deficiencies in internal controls in a timely manner or otherwise comply with the requirements of Section 404 in a timely manner, our ability to record, process, summarize and report financial information accurately and within applicable time periods may be adversely affected, and we could be subject to sanctions or investigations by the SEC, the Nasdaq Stock Market or other regulatory authorities as well as stockholder litigation which, even if resolved in our favor, would require additional financial and management resources and could adversely affect the market price of our common stock.
If we are not able to correct material weaknesses or deficiencies in internal controls in a timely manner or otherwise comply with the requirements of Section 404 in a timely manner, our ability to record, process, summarize and report financial information accurately and within applicable time periods may be adversely affected, and we could be subject to sanctions or investigations by the Securities Exchange Commission, or the SEC , the Nasdaq Stock Market or other regulatory authorities as well as stockholder litigation which, even if resolved in our favor, would require additional financial and management resources and could adversely affect the market price of our common stock.
Our preclinical studies and clinical trials may take longer to complete than currently anticipated, or may be delayed, suspended, required to be repeated, prematurely terminated or may not successfully demonstrate safety and/or efficacy needed to obtain or maintain regulatory approval for a variety of other reasons, such as: • the costs may be greater than we anticipate; • the number of patients required for clinical trials may be larger than we anticipate; • enrollment in our clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate; • our third party contractors, such as our CROs, may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all, or we may fail to communicate effectively or provide the appropriate level of oversight of such third party contractors; • the supply or quality of our starting materials, drug substance and drug product necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; • regulators, independent data monitoring committees, or IDMCs , institutional review boards, or IRBs , safety committees, or ethics committees, may require that we suspend or terminate our clinical trials for various reasons, including noncompliance with regulatory requirements, unforeseen safety issues or adverse side effects, failure to Akebia Therapeutics, Inc. | Form 10-K | Page 66 Table of Content s demonstrate a benefit from using our product candidate, or a finding that the participants are being exposed to unacceptable health risks; • clinical trials of our product candidates may produce negative or inconclusive results or results that may be interpreted in a manner different than we interpret them, and we may decide, or regulators may require us, to conduct additional clinical trials, repeat a clinical trial or abandon product development programs; • lack of adequate funding to continue a clinical trial, including unforeseen costs due to enrollment delays, requirements to conduct additional clinical trials or repeat a clinical trial and increased expenses associated with the services of our CROs and other third parties; • we may fail to initiate, delay of or failure to complete a clinical trial as a result of an Investigational New Drug application, or IND , being placed on clinical hold by the FDA, the EMA, the PMDA, or other regulatory authorities, or for other reasons, such as failure to recruit or enroll suitable patients or patients' failure to return for post-treatment follow up; • we may determine to change or expand a clinical trial, including after it has begun; • clinical trial sites and investigators deviating from the clinical protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial, or failure by us or our CROs to communicate effectively or provide the appropriate level of oversight of such clinical sites and investigators; • there may be an inability, delay, or failure in identifying and maintaining a sufficient number of clinical trial sites, many of which may already be engaged in other clinical programs; • there may be a delay or failure in reaching agreement with the FDA, the EMA, the PMDA or other regulatory authorities on a clinical trial design upon which we are able to execute; • there may be a delay or failure in obtaining authorization to commence a clinical trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial; • there may be delays in reaching, or failure to reach, agreement on acceptable terms with prospective clinical trial sites and prospective CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • the FDA, the EMA, the PMDA or other regulatory authorities may require us to submit additional data or impose further requirements before permitting us to initiate a clinical trial or during an ongoing clinical trial; • the FDA, the EMA, the PMDA or other regulatory authorities may disagree with our clinical trial design and our interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design for our clinical trials; • third parties with which we work may fail to comply with good practice quality guidelines and regulations, or GxP , including good laboratory practice, good clinical practice, or GCP , and current good manufacturing practice, or cGMP ; or • there may be changes in governmental regulations or administrative actions.
Akebia Therapeutics, Inc. | Form 10-K | Page 64 Table of Contents Our preclinical studies and clinical trials may take longer to complete than currently anticipated, or may be delayed, suspended, required to be repeated, prematurely terminated or may not successfully demonstrate safety and/or efficacy needed to obtain or maintain regulatory approval for a variety of other reasons, such as: • the costs may be greater than we anticipate; • the number of patients required for clinical trials may be larger than we anticipate; • enrollment in our clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate; • our third party contractors, such as our contract research organizations, or CROs , may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all, or we may fail to communicate effectively or provide the appropriate level of oversight of such third party contractors; • the supply or quality of our starting materials, drug substance and drug product necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; • regulators, independent data monitoring committees, institutional review boards, safety committees, or ethics committees, may require that we suspend or terminate our clinical trials for various reasons, including noncompliance with regulatory requirements, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using our product candidate, or a finding that the participants are being exposed to unacceptable health risks; • clinical trials of our product candidates may produce negative or inconclusive results or results that may be interpreted in a manner different than we interpret them, and we may decide, or regulators may require us, to conduct additional clinical trials, repeat a clinical trial or abandon product development programs; • lack of adequate funding to continue a clinical trial, including unforeseen costs due to enrollment delays, requirements to conduct additional clinical trials or repeat a clinical trial and increased expenses associated with the services of our CROs and other third parties; • we may fail to initiate, delay or fail to complete a clinical trial as a result of an Investigational New Drug application, or IND , being placed on clinical hold by the FDA, the EMA, the PMDA, or other regulatory authorities, or for other reasons, such as failure to recruit or enroll suitable patients or patients' failure to return for post-treatment follow up; • we may determine to expand or otherwise change a clinical trial, including after it has begun; • clinical trial sites and investigators deviating from the clinical protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial, or failure by us or our CROs to communicate effectively or provide the appropriate level of oversight of such clinical sites and investigators; • there may be an inability, delay, or failure in identifying and maintaining a sufficient number of clinical trial sites, many of which may already be engaged in other clinical programs; • there may be a delay or failure in reaching agreement with the FDA, the EMA, the PMDA or other regulatory authorities on a clinical trial design upon which we are able to execute; • there may be a delay or failure in obtaining authorization to commence a clinical trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial; • there may be delays in reaching, or failure to reach, agreement on acceptable terms with prospective clinical trial sites and prospective CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • the FDA, the EMA, the PMDA or other regulatory authorities may require us to submit additional data or impose further requirements before permitting us to initiate a clinical trial or during an ongoing clinical trial; • the FDA, the EMA, the PMDA or other regulatory authorities may disagree with our clinical trial design and our interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design for our clinical trials; • third parties with which we work may fail to comply with good practice quality guidelines and regulations, or GxP , including good laboratory practice, good clinical practice, or GCP , and current good manufacturing practice, or cGMP ; or • there may be changes in governmental regulations or administrative actions.
The incidence of TEAEs during the ESA-treated patients study (Conversion) in vadadustat treated patients was 89.1% and 87.7% in darbepoetin alfa-treated patients. During the study, the most common TEAEs reported in vadadustat/darbepoetin alfa-treated patients were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract infection (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%).
The incidence of TEAEs during the ESA-treated patients study (Conversion) in Vafseo-treated patients was 89.1% and 87.7% in darbepoetin alfa-treated patients. During the study, the most common TEAEs reported in Vafseo/darbepoetin alfa-treated patients were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract infection (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%).
In addition, any post-marketing clinical trials conducted, if successful, may expand the patient populations treated with Auryxia, vadadustat or any other product we acquire or for which we receive marketing approval, within or outside of their current indications or patient populations, which could result in the identification of previously unknown undesirable effects, increased frequency or severity of known undesirable effects, or result in the identification of unexpected safety signals.
In addition, any post-marketing clinical trials conducted, if successful, may expand the patient populations treated with Auryxia, Vafseo or any other product we acquire or for which we receive marketing approval, within or outside of their current indications or patient populations, which could result in the identification of previously unknown undesirable effects, increased frequency or severity of known undesirable effects, or result in the identification of unexpected safety signals.
Furthermore, others may independently develop similar or alternative drug products or technologies or design around our patented drug product and technologies which may have an adverse effect on our business.
Furthermore, others may independently develop similar or alternative drug products or technologies or design around our patented drug products and technologies which may have an adverse effect on our business.
Furthermore, certain companies are developing potential new therapies for renal-related diseases that could potentially reduce injectable erythropoiesis stimulating agent, or ESA, utilization and thus limit the market potential for vadadustat if they are approved and launched commercially. Other new therapies are in development for the treatment of conditions inclusive of renal anemia that may impact the market for anemia-targeted treatment.
Furthermore, certain companies are developing potential new therapies for renal-related diseases that could potentially reduce injectable erythropoiesis stimulating agent, or ESA, utilization and thus limit the market potential for Vafseo if they are approved and launched commercially. Other new therapies are in development for the treatment of conditions inclusive of renal anemia that may impact the market for anemia-targeted treatment.
Serious TEAEs were slightly lower for vadadustat treated patients at 55.0% and 58.3% for darbepoetin alfa-treated patients. Patients with DD-CKD experienced an increased risk of thromboembolic events compared to darbepoetin alfa with a time to first event HR of 1.20 (95% CI 0.96 - 1.50) driven by thrombosis of vascular access.
Serious TEAEs were slightly lower for Vafseo-treated patients at 55.0% and 58.3% for darbepoetin alfa-treated patients. Patients with DD-CKD experienced an increased risk of thromboembolic events compared to darbepoetin alfa with a time to first event HR of 1.20 (95% CI 0.96 — 1.50) driven by thrombosis of vascular access.
This review consisted of a blinded re-assessment of hepatic events conducted by a separate panel of hepatic experts. While hepatocellular injury attributed to vadadustat was reported in less than 1% of patients, there was one case of severe hepatocellular injury with jaundice, and we cannot guarantee that similar events will not happen in the future.
This review consisted of a blinded re-assessment of hepatic events conducted by a separate panel of hepatic experts. While hepatocellular injury attributed to Vafseo was reported in less than 1% of patients, there was one case of severe hepatocellular injury with jaundice, and we cannot guarantee that similar events will not happen in the future.
The third parties upon whom we rely may fail to perform effectively, or terminate their engagement with us, for a number of reasons, including the following: • if they experience staffing difficulties; • if we fail to communicate effectively or provide the appropriate level of oversight; Akebia Therapeutics, Inc. | Form 10-K | Page 88 Table of Content s • if they undergo changes in priorities or corporate structure including as a result of a merger or acquisition or other transaction, or become financially distressed; or • if they form relationships with other entities, some of which may be our competitors.
The third parties upon whom we rely may fail to perform effectively, or terminate their engagement with us, for a number of reasons, including the following: Akebia Therapeutics, Inc. | Form 10-K | Page 88 Table of Contents • if they experience staffing difficulties; • if we fail to communicate effectively or provide the appropriate level of oversight; • if they undergo changes in priorities or corporate structure including as a result of a merger or acquisition or other transaction, or become financially distressed; or • if they form relationships with other entities, some of which may be our competitors.
In addition, results of our clinical trials could reveal a high frequency of undesirable effects or unexpected characteristics. For example, in March 2022, we received the CRL from the FDA for our NDA for vadadustat in which the FDA concluded that the data in the NDA did not support a favorable benefit-risk assessment of vadadustat for dialysis and non-dialysis patients.
In addition, results of our clinical trials could reveal a high frequency of undesirable effects or unexpected characteristics. For example, in March 2022, we received the CRL from the FDA for our NDA for Vafseo in which the FDA concluded that the data in the NDA did not support a favorable benefit-risk assessment of Vafseo for dialysis and non-dialysis patients.
The delays and costs associated with the qualification of a new manufacturer and validation of manufacturing processes would negatively affect our ability to supply clinical trials, obtain and maintain marketing approval, or commercialize or satisfy patient demand for Auryxia and vadadustat, where approved, in a timely manner, within budget, or at all.
The delays and costs associated with the qualification of a new manufacturer and validation of manufacturing processes would negatively affect our ability to supply clinical trials, obtain and maintain marketing approval, or commercialize or satisfy patient demand for Auryxia and Vafseo, where approved, in a timely manner, within budget, or at all.
If the process validation is unsuccessful, or takes longer than we anticipate, we may have to expend additional resources and could experience a supply interruption. Any future supply interruptions, whether quality or quantity based, for Auryxia or vadadustat, if and where approved, would negatively and materially impact our reputation and financial condition.
If the process validation is unsuccessful, or takes longer than we anticipate, we may have to expend additional resources and could experience a supply interruption. Any future supply interruptions, whether quality or quantity based, for Auryxia or Vafseo where approved, would negatively and materially impact our reputation and financial condition.
Further, state Medicaid programs may be slow to invoice pharmaceutical companies for calculated rebates resulting in a lag between the time a sale is recorded and the time the rebate is paid. This results in us having to carry a liability on our consolidated balance sheets for the estimate of rebate claims expected for Medicaid patients.
Further, state Medicaid programs may be slow to invoice pharmaceutical companies for calculated rebates resulting in a lag between the time a sale is recorded and the time the rebate is paid. This results in us having to carry a liability on our consolidated balance sheet for the estimate of rebate claims expected for Medicaid patients.
In addition, the terms of the BlackRock Credit Agreement preclude us from paying cash dividends without prior written consent of the lender and future debt agreements may preclude us from paying cash dividends. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future. Item 1B.
In addition, the terms of the BlackRock Credit Agreement preclude us from paying cash dividends without prior written consent of the lender and future debt agreements may preclude us from paying cash dividends. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future.
If our third party manufacturers cannot successfully manufacture material that conforms to our specifications and regulatory requirements and guidance, or if we or our third party manufacturers experience manufacturing, operations and/or quality issues, including an inability or unwillingness to continue manufacturing our products at all, in accordance with agreed-upon processes or on currently validated manufacturing lines, we may not be able to supply patient demand or maintain marketing approval for Auryxia, secure and maintain marketing approval for vadadustat, and we might be required to expend additional resources to obtain material from other manufacturers.
If our third party manufacturers cannot successfully manufacture material that conforms to our specifications and regulatory requirements and guidance, or if we or our third party manufacturers experience manufacturing, operations and/or quality issues, including an inability or unwillingness to continue manufacturing our products at all, in accordance with agreed-upon processes or on currently validated manufacturing lines, we may not be able to supply patient demand or maintain marketing approval for Auryxia or Vafseo, and we might be required to expend additional resources to obtain material from other manufacturers.
In addition, Auryxia, Vafseo and vadadustat may compete with other products and product candidates for access to third party manufacturing facilities. A third party manufacturer or distributor may also encounter delays or operational issues brought on by sudden internal resource constraints, labor disputes, shifting priorities or shifting regulatory protocols.
In addition, Auryxia, Vafseo and our product candidates may compete with other products and product candidates for access to third party manufacturing facilities. A third party manufacturer or distributor may also encounter delays or operational issues brought on by sudden internal resource constraints, labor disputes, shifting priorities or shifting regulatory protocols.
Our collaboration, license and other revenue also depends on our partners’ ability to successfully market and sell vadadustat and Auryxia in the territories in which they have licensed our products. For example, in May 2023, we entered into a license agreement with MEDICE Arzneimittel Pütter GmbH & Co.
Our collaboration, license and other revenue also depends on our partners’ ability to successfully market and sell Vafseo and Auryxia in the territories in which they have licensed our products. For example, in May 2023, we entered into a license agreement with MEDICE Arzneimittel Pütter GmbH & Co.
This could impair our ability to successfully commercialize our product candidates and may harm our business and results of operations. We may find it difficult to enroll patients in our clinical trials, which could delay or prevent clinical trials of Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired.
This could impair our ability to successfully commercialize our product candidates and may harm our business and results of operations. We may find it difficult to enroll patients in our clinical trials, which could delay or prevent clinical trials of Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired.
Coverage and reimbursement by a governmental authority, third-party payor or PBMs may depend upon a number of factors, including the determination that use of a product is: • a covered benefit under the health plan; • safe, effective and medically necessary; • appropriate for the specific patient; and • cost effective.
Coverage and reimbursement by a governmental authority, dialysis organization, third-party payor or PBMs may depend upon a number of factors, including the determination that use of a product is: • a covered benefit under the health plan; • safe, effective and medically necessary; • appropriate for the specific patient; and • cost effective.
Obtaining coverage and reimbursement approval for a product from a governmental authority, PBM or a third-party payor is a time consuming and costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to the payor.
Obtaining coverage and reimbursement approval for a product from a governmental authority, dialysis organization, PBM or a third-party payor is a time consuming and costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to the payor.
We decided beginning in 2022 to terminate certain Part D contracts, as patients no longer had the access benefit given the prior authorization, or PA , requirement. Now p atients must go through a medical exemption process, which is very similar to a prior authorization review.
We decided beginning in 2022 to terminate certain Part D contracts, as patients no longer had the access benefit given the prior authorization requirement. Now p atients must go through a medical exemption process, which is very similar to a prior authorization review.
For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, Congress required sponsors to develop and submit a diversity action plan for each phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.
For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA , Congress required sponsors to develop and submit a diversity action plan, or DAP , for each phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.
We also utilize third parties for the commercial distribution of Auryxia, including wholesale distributors and certain specialty pharmacy providers.
We also utilize third parties for the commercial distribution of Auryxia and Vafseo, including wholesale distributors and certain specialty pharmacy providers.
Parties making claims against us or our licensees may seek and obtain injunctive or other equitable relief, which could effectively block our or their ability to continue to commercialize Auryxia or further develop and commercialize vadadustat or any other product candidates, including those that may be in-licensed or acquired.
Parties making claims against us or our licensees may seek and obtain injunctive or other equitable relief, which could effectively block our or their ability to continue to commercialize Auryxia or Vafseo or further develop and commercialize any product candidates, including those that may be in-licensed or acquired.
For example, any sustained disruption in the capital markets from adverse macroeconomic conditions and an uncertain geopolitical environment, such as rising inflation, increasing interest rates, slower economic growth or recession, global supply chain disruptions, the ongoing Russia-Ukraine war, the war in the Middle East and tensions between China and Taiwan, could negatively impact our ability to raise capital, and we cannot predict the extent or duration of such macroeconomic disruptions.
For example, any sustained disruption in the capital markets from adverse macroeconomic conditions and an uncertain geopolitical environment, such as rising inflation, increasing interest rates, slower economic growth or recession, global supply chain disruptions, the Russia-Ukraine war, the Israel-Hamas war and the war in the Middle East and tensions between China and Taiwan, could negatively impact our ability to raise capital, and we cannot predict the extent or duration of such macroeconomic disruptions.
Any of these events could prevent us from achieving or maintaining, whether on a restricted basis or at all, marketing approval and, ultimately, market acceptance or penetration of Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired.
Any of these events could prevent us from achieving or maintaining, whether on a restricted basis or at all, marketing approval and, ultimately, market acceptance or penetration of Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired.
The incidence of TEAEs during the prevalent dialysis patient study ( Conversion ) in the vadadustat treated patients was 88.3%, and 89.3% in darbepoetin alfa treated patients. During the study, the most common TEAEs reported in vadadustat/darbepoetin alfa treated patients were diarrhea (13.0%/ 10.1%), pneumonia (11.0%/ 9.7%), hypertension (10.6%/ 13.8%), and hyperkalemia (9.0%/ 10.8%).
The incidence of TEAEs during the prevalent dialysis patient study (Conversion) in the Vafseo-treated patients was 88.3%, and 89.3% in darbepoetin alfa treated patients. During the study, the most common TEAEs reported in Vafseo/darbepoetin alfa treated patients were diarrhea (13.0%/ 10.1%), pneumonia (11.0%/ 9.7%), hypertension (10.6%/ 13.8%), and hyperkalemia (9.0%/ 10.8%).
Such litigation would subject us to additional litigation costs, damages and reputational harm, which could lead to lower revenues. The CREATES Act may facilitate future competition with Auryxia and any of our product candidates, if approved, which could impact our ability to maximize product revenue.
Such litigation would subject us to additional litigation costs, damages and reputational harm, which could lead to lower revenues. The CREATES Act may facilitate future competition with Auryxia or Vafseo and any of our product candidates, if approved, which could impact our ability to maximize product revenue.
The patent rights and related non-patent exclusivity that we own or have licensed relating to Auryxia, vadadustat, or other future products, are, or may be limited in ways that may affect our ability to exclude third parties from competing against us.
The patent rights and related non-patent exclusivity that we own or have licensed relating to Auryxia, Vafseo or other future products, are, or may be limited in ways that may affect our ability to exclude third parties from competing against us.
In addition, vadadustat was approved in Japan for the treatment of adult patients with anemia due to CKD and is being marketed by MTPC in Japan under the trade name Vafseo. Pricing and reimbursement strategy is a key component of MTPC’s commercialization plans for Vafseo in Japan.
Vafseo was approved in Japan for the treatment of adult patients with anemia due to CKD and is being marketed by MTPC in Japan under the trade name Vafseo. Pricing and reimbursement strategy is a key component of MTPC’s commercialization plans for Vafseo in Japan.
With respect to the global INNO 2 VATE Phase 3 program, the incidence of treatment emergent adverse events, or TEAEs , during the Correction and Conversion study in vadadustat treated patients was 83.8% and 85.5% in darbepoetin alfa treated patients.
With respect to the global INNO 2 VATE Phase 3 program, the incidence of treatment emergent adverse events, or TEAEs , during the Correction and Conversion study in Vafseo-treated patients was 83.8% and 85.5% in darbepoetin alfa treated patients.
In December 2019, former President Trump signed legislation intended to facilitate the development of generic and biosimilar products.
In December 2019, President Trump signed legislation intended to facilitate the development of generic and biosimilar products.
For example, during the conduct of our Phase 3 program our team and hepatic experts analyzed hepatic cases (unblinded to treatment) and, following the completion of our global Phase 3 clinical program for vadadustat, there was a review of hepatic safety across the vadadustat clinical program, which included eight completed Phase 2 and 3 studies in NDD-CKD patients, 10 completed Phase 1, 2, and 3 studies, and two then-ongoing Phase 3b studies in DD-CKD patients, and 18 completed studies in healthy subjects (17 Phase 1 and one Phase 3).
During the conduct of our Phase 3 program for Vafseo, our team and hepatic experts analyzed hepatic cases (unblinded to treatment) and, following the completion of our global Phase 3 clinical program for Vafseo, there was a review of hepatic safety across the Vafseo clinical program, which included eight completed Phase 2 and 3 studies in NDD-CKD patients, 10 completed Phase 1, 2, and 3 studies, and two then-ongoing Phase 3b studies in DD-CKD patients, and 18 completed studies in healthy subjects (17 Phase 1 and one Phase 3).
Under the Royalty Agreement, we are required to comply with various covenants, including obligations to take certain actions, such as actions with respect to the Royalty Interest Payments, the MTPC Agreement, our agreement with MTPC for the commercial supply of vadadustat drug product, and our intellectual property.
Under the Royalty Agreement, we are required to comply with various covenants, including obligations to take certain actions, such as actions with respect to the Royalty Interest Payments, the MTPC Agreement, our agreement with MTPC for the commercial supply of Vafseo drug product, and our intellectual property.
If Medice is not able to obtain favorable pricing in the Medice Territory, or if such approvals are delayed, it will affect Medice’s sales of vadadustat in the Medice Territory, which could have an adverse effect on our results of operations.
If Medice is not able to obtain favorable pricing in the Medice Territory, or if such approvals are delayed, it will affect Medice’s sales of Vafseo in the Medice Territory, which could have an adverse effect on our results of operations.
Also, if our starting materials, drug substance or drug product are damaged or lost while in our or our third party manufacturers’ or distributors' control, it may adversely impact our ability to supply Auryxia or vadadustat, and we may incur significant financial harm.
Also, if our starting materials, drug substance or drug product are damaged or lost while in our or our third party manufacturers’ or distributors' control, it may adversely impact our ability to supply Auryxia or Vafseo, and we may incur significant financial harm.
An adverse ruling in any litigation or administrative proceeding could prevent us or our partners from marketing and selling Auryxia, Vafseo or vadadustat, if approved, or other future products, increase the risk that a generic or other similar version of Auryxia, Vafseo or vadadustat, if approved, or other future products could enter the market to compete with Auryxia, Vafseo or vadadustat, if approved, or other future products, limit our or our partners' development and commercialization of Auryxia, Vafseo or vadadustat, if approved, or other future products, or otherwise harm our competitive position and result in additional significant costs.
An adverse ruling in any litigation or administrative proceeding could prevent us or our partners from marketing and selling Auryxia, Vafseo or other future products, increase the risk that a generic or other similar version of Auryxia, Vafseo or other future products could enter the market to compete with Auryxia, Vafseo or other future products, limit our or our partners' development and commercialization of Auryxia, Vafseo or other future products, or otherwise harm our competitive position and result in additional significant costs.
In addition, any of these events could substantially increase our costs, and could significantly impact our ability to successfully commercialize Auryxia, vadadustat or any other product and product candidate, including those that may be in-licensed or acquired, and generate product revenue.
In addition, any of these events could substantially increase our costs, and could significantly impact our ability to successfully commercialize Auryxia, Vafseo or any other product and product candidate, including those that may be in-licensed or acquired, and generate product revenue.
Moreover, our failure or the failure of our third party manufacturers or distributors to comply with applicable regulations or guidance, or our failure to oversee or facilitate such compliance, could result in sanctions being imposed on us or our third party manufacturers or distributors, including, where applicable, clinical holds, fines, injunctions, civil penalties, delays in, suspension of or withdrawal of approvals, license revocation, seizures or recalls of Auryxia or Vafseo in Japan, operating restrictions, receipt of a Form 483 or warning letter, or criminal prosecutions, any of which could significantly and adversely affect the supply of Auryxia or vadadustat.
Moreover, our failure or the failure of our third party manufacturers or distributors to comply with applicable regulations or guidance, or our failure to oversee or facilitate such compliance, could result in sanctions being imposed on us or our third party manufacturers or distributors, including, where applicable, clinical holds, fines, injunctions, civil penalties, delays in, suspension of or withdrawal of approvals, license revocation, seizures or recalls of Auryxia or Vafseo in the U.S., Japan or Europe, operating restrictions, receipt of a Form 483 or warning letter, or criminal prosecutions, any of which could significantly and adversely affect the supply of Auryxia or Vafseo.
Our future financial performance and our ability to commercialize Auryxia and vadadustat, if and where approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively. This future growth will impose significant added responsibilities on the business and members of management.
Our future financial performance and our ability to commercialize Auryxia and Vafseo, if and where approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively. This future growth will impose significant added responsibilities on the business and members of management.
In addition, our current and any future collaborations may not be successful due to a number of important factors, including the following: • collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; Akebia Therapeutics, Inc. | Form 10-K | Page 84 Table of Content s • collaborations may be terminated in accordance with the terms of the collaboration agreements and, if terminated, may make it difficult for us to attract new collaborators or adversely affect how we are perceived in scientific and financial communities, and may result in a need for additional capital and expansion of our internal capabilities to pursue further development or commercialization of the applicable products and product candidates; • if permitted by the terms of the collaboration agreements, collaborators may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus, availability of funding or other external factors such as a business combination that diverts resources or creates competing priorities; • if permitted by the terms of the collaboration agreements, collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • a collaborator with marketing and distribution rights to our products may not commit sufficient resources to their marketing and distribution; • if permitted by the terms of the collaboration agreements, we and our collaborator may have a difference of opinion regarding the development or commercialization strategy for a particular product or product candidate, and our collaborator may have ultimate decision making authority; • disputes may arise between a collaborator and us that cause the delay or termination of activities related to research, development, supply or commercialization of Auryxia, Riona, Vafseo or vadadustat and any other product candidate, or that result in costly litigation or arbitration that diverts management attention and resources; • collaborations may not lead to development or commercialization of products and product candidates, if approved, in the most efficient manner or at all; • inefficiencies or structural changes in internal operations or processes of our collaborators may lead to increased expenses associated with commercializing a product, including manufacturing costs, rebates, returns and other adjustments which would negatively impact net product revenue; • a significant change in the senior management team, a change in the financial condition or a change in the business operations, including a change in control or internal corporate restructuring, of any of our collaborators, could result in delayed timelines, re-prioritization of our programs, decreasing resources or funding allocated to support our programs, or termination of the collaborations; and • collaborators may not comply with all applicable regulatory and legal requirements.
In addition, our current and any future collaborations may not be successful due to a number of important factors, including the following: • collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborations may be terminated in accordance with the terms of the collaboration agreements and, if terminated, may make it difficult for us to attract new collaborators or adversely affect how we are perceived in scientific and financial communities, and may result in a need for additional capital and expansion of our internal capabilities to pursue further development or commercialization of the applicable products and product candidates; • if permitted by the terms of the collaboration agreements, collaborators may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus, availability of funding or other external factors such as a business combination that diverts resources or creates competing priorities; • if permitted by the terms of the collaboration agreements, collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • a collaborator with marketing and distribution rights to our products may not commit sufficient resources to their marketing and distribution; • if permitted by the terms of the collaboration agreements, we and our collaborator may have a difference of opinion regarding the development or commercialization strategy for a particular product or product candidate, and our collaborator may have ultimate decision making authority; • disputes may arise between a collaborator and us that cause the delay or termination of activities related to research, development, supply or commercialization of Auryxia, Riona or Vafseo and any other product candidate, or that result in costly litigation or arbitration that diverts management attention and resources; • collaborations may not lead to development or commercialization of products and product candidates, if approved, in the most efficient manner or at all; • inefficiencies or structural changes in internal operations or processes of our collaborators may lead to increased expenses associated with commercializing a product, including manufacturing costs, rebates, product returns and other adjustments which would negatively impact net product revenue; • a significant change in the senior management team, a change in the financial condition or a change in the business operations, including a change in control or internal corporate restructuring, of any of our collaborators, could result in delayed timelines, re-prioritization of our programs, decreasing resources or funding allocated to support our programs, or termination of the collaborations; and • collaborators may not comply with all applicable regulatory and legal requirements.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAkebia Therapeutics, Inc. | Form 10-K | Page 105 Table of Content s • Third-Party Risk Management — We maintain a risk-based approach to identifying and overseeing material cybersecurity threats presented by third parties and the systems of third parties that could adversely impact our business in the event of a material cybersecurity incident affecting those third-party systems. • Education and Awareness — We provide training regarding cybersecurity threats as a means to equip our employees and consultants with tools to make employees and consultants aware of and to address cybersecurity threats, and to communicate our evolving information security policies, standards, processes and practices.
Biggest changeAlso, we engage certain external cybersecurity firms to enhance our cybersecurity oversight and cybersecurity breach detection over third party service providers. • Education and Awareness — We provide training regarding cybersecurity threats as a means to equip our employees and consultants with tools to make employees and consultants aware of and to address cybersecurity threats, and to communicate our evolving information security policies, standards, processes and practices.
Such processes include (i) procedural and technical safeguards, (ii) response plans, (iii) annual tests on our systems, (iv) incident simulations and (v) routine review of our cybersecurity policies and procedures to identify risks and improve our practices. We engage certain external cybersecurity firms to enhance our cybersecurity oversight.
Such processes include (i) procedural and technical safeguards, (ii) response plans, (iii) periodic tests on our systems, (iv) incident simulations and (v) routine review of our cybersecurity policies and procedures to identify risks and improve our practices. We engage certain external cybersecurity firms to enhance our cybersecurity oversight.
Through ongoing communications with this management committee, senior management is informed about and monitors the prevention, detection, mitigation and remediation of cybersecurity threats and incidents in real-time and reports such threats and incidents to the Audit Committee, when appropriate. Management updates the Audit Committee quarterly with an overview of our cybersecurity threat risk management and strategy processes.
Through ongoing communications with this management committee, senior management is informed about and monitors the prevention, detection, mitigation and remediation of cybersecurity threats and incidents in real-time and reports such threats and incidents to the Audit Committee, when appropriate. Management updates the Audit Committee quarterly regarding our cybersecurity threat risk management and strategy programs.
We use an internal management committee to run our information and technology team and our information and technology team includes our cybersecurity team lead who has served in various roles in information technology and information security for over 25 years, including at other public companies.
We use an internal management team to run our information technology and cybersecurity functions, which includes our information and cybersecurity team leads who have collectively served in various roles in information technology and information security for over 25 years, including at other public companies.
Members of the Audit Committee are also encouraged to regularly engage in ad hoc conversations with management on cybersecurity-related topics and discuss any updates to our cybersecurity risk management and strategy programs.
Members of the Audit Committee are also encouraged to regularly engage in ad hoc Akebia Therapeutics, Inc. | Form 10-K | Page 106 Table of Contents conversations with management on cybersecurity-related topics and discuss any updates to our cybersecurity risk management and strategy programs.
The Audit Committee of our Board of Directors meets annually to discuss our approach to overseeing cybersecurity threats with management, including with members of our internal cybersecurity team.
The Audit Committee reports to the Board of Directors at least annually, and notifies the Board of Directors as necessary regarding significant new cybersecurity threats or incidents. The Audit Committee meets annually to discuss our approach to overseeing cybersecurity threats with management, including with members of our internal cybersecurity team.
While the full Board of Directors has overall responsibility for risk oversight, the Board of Directors has delegated oversight responsibility related to risks from cybersecurity threats to the Audit Committee. The Audit Committee reports to the Board of Directors at least annually, and notifies the Board of Directors as necessary regarding significant new cybersecurity threats or incidents.
While the full Board of Directors has overall responsibility for risk oversight, the Board of Directors has delegated oversight responsibility related to risks from cybersecurity threats to the Audit Committee of our Board of Directors.
We conduct regular tabletop exercises, including incident simulations to test these plans and ensure personnel are familiar with their roles and responsibilities in a response scenario.
We conduct periodic tabletop exercises, including incident simulations to test these plans and ensure personnel are familiar with their roles and responsibilities in a response scenario. • Third-Party Risk Management — We maintain a risk-based approach to identifying and overseeing material cybersecurity threats presented by third parties and the systems of third parties that could adversely impact our business in the event of a material cybersecurity incident affecting those third-party systems.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeIn the third quarter of 2022, as a result of the reductions in our workforce and our transition to primarily hybrid and remote work schedules, we ceased using two-thirds of the office space, and began to market up to 59,216 square feet of furnished office space for sublease. We believe our existing facilities are adequate to meet our operational needs.
Biggest changeDue to our primarily hybrid workforce, we are marketing up to 59,216 square feet of furnished office space for sublease. We believe our existing facilities are adequate to meet our operational needs.
Item 2. Properties We currently lease approximately 65,167 square feet of office, storage and laboratory space in Cambridge, Massachusetts, which is our corporate headquarters. Excluding renewal options, the lease for our Cambridge, Massachusetts office and storage space expires on September 11, 2026 and the lease for our laboratory space expires on January 31, 2025.
Item 2. Properties We currently lease approximately 65,167 square feet of office, storage and laboratory space in Cambridge, Massachusetts, which is our corporate headquarters. Excluding renewal options, the lease for our Cambridge, Massachusetts office, storage and lab space expires on September 11, 2026.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeAkebia Therapeutics, Inc. | Form 10-K | Page 106 Table of Content s On July 26, 2022, Sandoz AG filed an opposition against our issued European Patent No. 3277270 in the European Patent Office, or the EPO . During an oral proceeding held on February 6, 2024, the EPO's Opposition Division rejected the opposition and upheld the patent as granted.
Biggest changeOn November 6, 2024, Sandoz AG filed an opposition against our issued European Patent No. 3007695 covering vadadustat once daily dosing regimen in the European Patent Office. Item 4. Mine Safety Disclosures Not applicable. Akebia Therapeutics, Inc. | Form 10-K | Page 107 Table of Contents PART II
Item 3. Legal Proceedings Opposition Proceedings Against Akebia In September 2018, Dr. Reddy’s Laboratories Limited filed an opposition to our issued Indian Patent No. 287720 in the Indian Patent Office.
Item 3. Legal Proceedings From time to time, we may be involved in legal proceedings arising from the normal course of business activities. Opposition Proceedings Against Akebia In September 2018, Dr. Reddy’s Laboratories Limited filed an opposition to our issued Indian Patent No. 287720 covering the composition of matter of vadadustat in the Indian Patent Office.
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Settled Opposition Proceedings Against Akebia On February 13, 2023, FibroGen, Inc., or FibroGen, filed an opposition against our issued European Patent No. 3357911, or the ’ 911 EP Patent , in the EPO.
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On November 21, 2023, we and our collaboration partner in Japan, Mitsubishi Tanabe Pharma Corporation, or MTPC , entered into a Settlement and Cross License Agreement, or the Settlement Agreement , with FibroGen and its collaboration partner in Europe and Japan, Astellas Pharma Inc., or Astellas .
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This Settlement Agreement resolves all patent disputes between Akebia, MTPC, FibroGen and Astellas in the EU, the contracting states to the European Patent Convention, the UK , and Japan with no cash payment. On November 22, 2023, FibroGen withdrew the opposition against the ’911 EP Patent pursuant to the terms of the Settlement Agreement.
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Settled Proceedings Filed by Akebia Against FibroGen Europe We filed an opposition in the EPO against FibroGen’s European Patent No. 1463823, or the ’823 EP Patent on December 5, 2013, and an oral proceeding took place March 8 and 9, 2016.
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Following the oral proceeding, the Opposition Division of EPO ruled that the patent as granted did not meet the requirements for patentability under the European Patent Convention and, therefore, revoked the patent in its entirety. FibroGen appealed that decision. On February 27, 2023, FibroGen withdrew its appeal, and the patent remains revoked.
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On April 3, 2019, we filed oppositions to FibroGen’s European Patent Nos. 2289531, or the ’531 EP Patent, and 2298301, or the ’301 EP Patent in the EPO, respectively, requesting the patents be revoked in their entirety. Oral proceedings for oppositions to the two patents were held on September 7, 8 and 10, 2021.
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Following oral proceedings, the Opposition Division of the EPO maintained certain claims in amended form in the two patents. On January 26, 2022, we filed notice to appeal the Opposition Division’s decision for ’531 EP Patent.
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On July 8, 2022, FibroGen filed notice to appeal the Opposition Division’s decision for the ’301 EP Patent, which it withdrew on August 17, 2022. On November 21, 2023, we withdrew our appeal to the Opposition Division’s decision for ’531 EP Patent pursuant to the terms of the Settlement Agreement.
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Japan In 2018, we and MTPC jointly filed a Request for Trial before the Japan Patent Office, or JPO to challenge the validity of certain of FibroGen’s HIF-related patents in Japan: JP4845728, JP5474872 and JP5474741. On September 26, 2019, the JPO conducted an invalidation trial for JP5474872 and JP4845728.
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On November 11, 2019, the JPO conducted an invalidation trial for JP5474741. On April 1, 2022, the JPO issued a final decision for JP4845728, which invalidated all claims except claims directed to the medical use to treat anemia that does not respond to erythropoiesis.
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On May 18, 2022, the JPO issued a final decision for JP5474741 and JP5474872, which maintained the claims in amended form. In May 2022, MTPC filed revocation lawsuits for the three patents in the Intellectual Property High Court requesting cancellation of the JPO’s decisions.
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In July 2022, we filed a revocation lawsuit for JP4845728 in the Intellectual Property High Court requesting cancellation of the JPO’s decision. In August 2022, we filed revocation lawsuits for JP5474741 and JP5474872 in the Intellectual Property High Court requesting cancellation of the JPO’s decisions.
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In September 2022, FibroGen filed a revocation lawsuit for JP4845728 in the Intellectual Property High Court requesting cancellation of the JPO’s decision on the claims that were invalidated.
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In November 2023, Akebia, MTPC, and FibroGen filed with the Japan Intellectual High Court written consent to withdraw the revocation lawsuits related to JP4845728, JP5474872 and JP5474741 pursuant to the terms of the Settlement Agreement.
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United Kingdom On December 13, 2018, we filed Particulars of Claim in the Patents Court of the United Kingdom to challenge the validity of FibroGen’s six HIF-related patents in the UK: the ’823 EP Patent (UK), European Patent (UK) No. 1633333, or the ’333 EP Patent (UK) , European Patent (UK) No. 2322153, or the ’153 EP Patent (UK), European Patent (UK) No. 2322155, or the ’155 EP Patent (UK) , European Patent (UK) No. 2,289,531, or the ’531 EP Patent (UK) , and European Patent (UK) No. 2,298,301, or the ’301 EP Patent (UK) .
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In May 2019, Astellas, the exclusive licensee of FibroGen’s HIF-related patents, sued Akebia for patent infringement in the Patents Court of the UK. In September 2019, we filed an Amended Particulars of Claim to include FibroGen’s European Patent No. 1487472, or the ’472 EP Patent (UK) .
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On February 28, 2020, the parties agreed to dismiss the ’472 EP Patent (UK) from the trial. A trial was conducted in March 2020.
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On April 20, 2020, the Patents Court of the UK issued a judgment in favor of Akebia, which invalidated all the claims at issue in each of the ’823 EP Patent (UK), the ’333 EP Patent (UK), the ’153 EP Patent (UK), the ’155 EP Patent (UK) and the ’301 EP Patent (UK).
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The ’531 EP Patent (UK) was amended to a single claim to recite one specific compound; this claim was held to be valid but not infringed by vadadustat.
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On June 11, 2020, FibroGen and Astellas appealed the Patents Court’s judgment on the invalidity of the ’823 EP Patent (UK), the ’301 EP Patent (UK), the ’333 EP Akebia Therapeutics, Inc. | Form 10-K | Page 107 Table of Content s Patent (UK), the ’153 EP Patent (UK), and the ’155 EP Patent (UK) in the Court of Appeal (Civil Division).
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On June 8, 2021 - June 10, 2021, the United Kingdom Court of Appeal held a three-day hearing for the appeal.
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On August 24, 2021, the Court of Appeal issued a judgment, which reversed the Patents Court’s judgment on the invalidity of the ’823 EP Patent (UK) and maintained certain claims of the ’823 EP Patent (UK) and the ’301 EP Patent (UK) in amended form, and which affirmed the Patents Court’s judgment on the invalidity of the ’333 EP Patent (UK), the ’155 EP Patent (UK), and the ’153 EP Patent (UK).
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Akebia sought permission to appeal to the UK Supreme Court, which was granted on October 3, 2022. On November 28, 2023, we filed an application for withdrawal of the Appeal at the UK Supreme Court pursuant to the terms of the Settlement Agreement. On December 15, 2023, the UK Supreme Court ordered that the Appeal be withdrawn.
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Legal Proceedings Relating to Auryxia Stockholder Litigation Relating to the Merger On June 28, 2018, we entered into an Agreement and Plan of Merger with Keryx and Alpha Therapeutics Merger Sub, Inc., or the Merger Sub, pursuant to which the Merger Sub merged with and into Keryx, with Keryx becoming a wholly owned subsidiary of ours, or the Merger.
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On December 12, 2018, we completed the Merger. On July 15, 2021, a purported former Keryx stockholder filed a putative class action in the Supreme Court of the State of New York against Akebia, a current officer of Akebia (John P. Butler), a former officer of Akebia (Jason A. Amello), former directors of Akebia (Muneer A. Satter, Scott A.
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Canute, Michael D. Clayman, Maxine Gowen, Duane Nash, Ronald C. Renaud, Jr., and Michael S. Wyzga), a current director of Akebia (Cynthia Smith), a former director and officer of Keryx (Jodie P. Morrison), a former officer of Keryx (Scott A. Holmes) and former directors of Keryx (Michael Rogers, Kevin J. Cameron, Steven C. Gilman, Daniel P. Regan, Mark J.
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Enyedy, and Michael T. Heffernan, some of whom are current members of our Board of Directors). The action is captioned Loper v. Akebia Therapeutics, Inc., et al., or the Loper Action .
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The complaint in the Loper Action alleges that the registration statement filed in connection with the Merger contained allegedly false and misleading statements or failed to disclose certain allegedly material information in violation of Section 11, 12(a)(2), and 15 of the Securities Act of 1933, as amended.
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It alleges, among other things, that Akebia failed to disclose heightened safety risks that allegedly threatened the prospects of the Phase 3 PRO2TECT clinical trial and the commercial viability of vadadustat.
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The complaint in the Loper Action seeks damages including interest thereon, an award of plaintiffs’ and the class’s costs and expenses, including counsel fees and expert fees, and rescission, disgorgement, or such other equitable or injunctive relief that the Court deems appropriate.
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On August 16, 2021, another purported former Keryx stockholder filed a putative class action making substantially similar allegations and asserting the same claims as the Loper Action, also in the Supreme Court of the State of New York against Akebia and many of the same individual defendants named in the Loper Action. The action is captioned Panicho v.
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Akebia Therapeutics, Inc., et al., or the Panicho Action. On September 13, 2021, the parties in the Loper Action and Panicho Action entered into a joint stipulation and proposed order, which provided for the consolidation of the two actions under the caption In re Akebia Therapeutics, Inc. Securities Litigation, or the Consolidated State Action.
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On October 27, 2021, plaintiffs filed a consolidated complaint in the Consolidated State Action. On January 10, 2022, defendants moved to dismiss the consolidated complaint in its entirety. Briefing on defendants’ motion to dismiss was completed on April 22, 2022.
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Oral argument was held on October 7, 2022, and the Court dismissed the complaint without prejudice on October 17, 2022, giving plaintiffs thirty days to amend their complaint. On November 16, 2022, plaintiffs filed an amended consolidated complaint, asserting the same claims and seeking the same relief as the consolidated complaint.
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On January 18, 2023, defendants moved to dismiss the amended consolidated complaint in its entirety, and the plaintiffs filed their opposition on March 6, 2023. Briefing on defendants’ motion to dismiss the amended consolidated complaint was completed on April 5, 2023. Oral argument was held on March 13, 2024.
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At the conclusion of the hearing, the Court granted our motion to dismiss. We deny any allegations of wrongdoing and intend to continue vigorously defending against the one active stockholder lawsuit described in this Legal Proceedings section, the Consolidated State Action.
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There is no assurance, however, that we will be successful in the defense of this action, or any associated appeals, or that insurance will be available or adequate to fund any settlement or judgment or the litigation costs of this action. Moreover, we are unable to predict the outcome or reasonably estimate a range of possible losses at this time.
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A resolution of the Consolidated State Action in a manner adverse to us, however, could have a material effect on our financial position and results of operations in the period in which the action is resolved.
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Settled ANDA Litigation In February 2023, we received a Paragraph IV certification notice letter regarding an Abbreviated New Drug Application, or ANDA, submitted to the U.S. Food and Drug Administration, or FDA, by Zydus Worldwide DMCC requesting approval for a generic version of Auryxia tablets (210 mg ferric iron per tablet).
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On March 24, 2023, we and Panion & BF Biotech, Inc., or Panion, filed a complaint for patent infringement against Zydus Worldwide DMCC, Zydus Pharmaceuticals (USA) Inc., and Zydus Lifesciences Limited, or collectively Zydus, in the United States District Court for the District of Delaware arising from Akebia Therapeutics, Inc. | Form 10-K | Page 108 Table of Content s Zydus’ ANDA filing with the FDA.
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On May 30, 2023, we and Panion entered into a settlement and license agreement with Zydus, which resolved the patent litigation brought by we and Panion.
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Such settlement and license agreement, consistent with our prior ANDA settlements, granted Zydus a license to market a generic version of Auryxia in the U.S. beginning on March 20, 2025 (subject to FDA approval), or earlier under certain circumstances customary for settlement agreements of this nature.
Removed
Additionally, in accordance with the settlement and license agreement, the parties terminated all ongoing litigation among us, Panion and Zydus regarding Auryxia patents pending in the Delaware District Court. The settlement and license agreement is confidential and subject to review by the U.S. Federal Trade Commission and the U.S. Department of Justice.
Removed
On June 5, 2023, the Delaware District Court entered a stipulation and order of dismissal filed by the parties to terminate the action against Zydus.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

3 edited+212 added−0 removed2 unchanged
Biggest changeIssuer Purchases of Equity Securities None. Recent Sales of Unregistered Securities None. Purchases of Equity Securities by the Issuer and Affiliated Purchasers None. Comparative Stock Performance Graph We are a smaller reporting company, as defined by Rule 12b-2 of the Exchange Act, and are not required to provide a stock performance graph.
Biggest changePurchases of Equity Securities by the Issuer and Affiliated Purchasers None. Comparative Stock Performance Graph We are a smaller reporting company, as defined by Rule 12b-2 of the Exchange Act, and are not required to provide a stock performance graph.
Securities Authorized for Issuance under Equity Compensation Plans Information about our equity compensation plans is incorporated herein by reference to Item 12, Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters , of this Form 10-K. Item 6. [Reserved]
Securities Authorized for Issuance under Equity Compensation Plans Information about our equity compensation plans is incorporated herein by reference to Item 12, Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters , of this Form 10-K. Item 6. [Reserved] Item 7.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock is traded on The Nasdaq Capital Market under the symbol “AKBA”. Holders At March 12, 2024, there were approximately 30 holders of record of our common stock.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock is traded on The Nasdaq Capital Market under the symbol “AKBA”. Holders At March 10, 2025, there were approximately 26 holders of record of our common stock.
Added
Issuer Purchases of Equity Securities None. Recent Sales of Unregistered Securities We did not sell any securities that were not registered under the Securities Act of 1933, as amended, or the Securities Act, during the year ended, other than pursuant to transactions previously disclosed in our Current Reports on Form 8-K.
Added
Management’s Discussion and Analysis of Financial Condition and Results of Operations This Annual Report on Form 10-K, or Form 10-K , including this management's discussion and analysis of financial condition and results of operations, contains forward-looking statements based upon current expectations that involve risks and uncertainties.
Added
Our actual results may differ materially from those described in or implied in these forward-looking statements as a result of various factors, including those factors set forth in the “Risk Factors” section included in Part I, Item 1A of this Form 10-K. All references to years, unless otherwise noted, refer to our fiscal years, which end on December 31.
Added
For purposes of this section, all references to “we,” “us,” “our,” “Akebia,” or the “Company” refer to Akebia Therapeutics, Inc. and its consolidated subsidiaries. The following discussion and analysis should also be read in conjunction with the accompanying audited consolidated financial statements and related notes included in Part II, Item 8 of this Form 10-K.
Added
This section discusses 2024 and 2023 financial condition, and results of operations and year-to-year comparisons between 2024 and 2023.
Added
For discussion of 2023 items and year-over-year comparisons between 2023 and 2022 that are not included in this 2024 Form 10-K, refer to “Item 7. – Management’s Discussion and Analysis of Financial Condition and Results of Operations” found in our Form 10-K for the year ended December 31, 2023, that was filed with the Securities and Exchange Commission on March 14, 2024.
Added
Business Overview We are a fully integrated, biopharmaceutical company with two commercial products for patients impacted by kidney disease. We have built a business focused on developing and commercializing innovative therapeutics that we believe serve as a foundation for future growth.
Added
Our team has significant expertise in hypoxia-inducible factor, or HIF , science having developed Akebia Therapeutics, Inc. | Form 10-K | Page 108 Table of Contents and commercialized Vafseo® (vadadustat), an oral HIF factor prolyl hydroxylase, or HIF-PH , inhibitor and have selected two additional HIF-based molecules for preclinical development.
Added
We have established the company as a leader in the kidney community, and we believe our cross-organizational expertise in renal disease positions the company for success. Chronic kidney disease, or CKD , is a condition in which the kidneys are progressively damaged to the point that they cannot properly filter the blood circulating in the body.
Added
This damage causes waste products to build up in the patient’s blood, leading to other health problems, including anemia, cardiovascular disease and bone disease.
Added
CKD significantly impacts the U.S. healthcare system, potentially affecting approximately 37 million patients and costing Medicare nearly $125 billion annually for treating Medicare beneficiaries with CKD or end-stage renal disease, or ESRD , according to the Centers for Disease Control and Prevention. Our two commercial products address certain complications of kidney disease.
Added
Our current portfolio includes: Vafseo was approved by the U.S. Food and Drug Administration, or the FDA , in March 2024 for the treatment of anemia due to CKD in adult patients on dialysis for at least three months. Shipment of Vafseo commenced in January 2025.
Added
We have commercial supply agreements for the purchase of Vafseo in place with dialysis organizations caring for nearly 100% of dialysis patients in the U.S.
Added
The current U.S. market opportunity for the treatment of anemia due to CKD in patients with dialysis is approximately $1 billion based on current ESA pricing and Vafseo is the only oral HIF-based treatment available in the U.S.
Added
In the European Union, or EU , the United Kingdom, or UK , Switzerland and Australia, Vafseo is approved for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis. Our partner MEDICE Arzneimittel Pütter GmbH & Co.
Added
KG, or Medice , has an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in defined territories and launched Vafseo in Germany, Austria, Switzerland, the Netherlands and certain other countries in Europe in 2024.
Added
In Japan, Vafseo is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent patients and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporation, or MTPC .
Added
In Taiwan, Vafseo is approved for the treatment of symptomatic anemia due to CKD in adult patients on chronic maintenance dialysis and launched in October 2024 by Tai Tien Pharmaceutical Company, an affiliate of MTPC. In Korea, Vafseo is approved as an anemia treatment for patients with CKD on hemodialysis.
Added
Auryxia® (ferric citrate) is an orally administered medicine approved and marketed in the U.S. for two indications: (1) the control of serum phosphorus levels in adult patients with dialysis dependent chronic kidney disease, or DD-CKD , and (2) the treatment of iron deficiency anemia, or IDA , in adult patients with non-dialysis-dependent chronic kidney disease, or NDD-CKD .
Added
Today, we market Auryxia in the U.S. Auryxia became part of our portfolio in 2018 and has historically contributed meaningful revenue to the business. In March 2025, Auryxia will lose exclusivity, or LoE .
Added
We believe the dynamics of Auryxia reimbursement being included in the ESRD bundle under Medicare Part B could result in slower revenue decline after the LoE date than in other LoE situations, but the impact of LoE on future Auryxia revenues will depend on many factors, including our ability to maintain contracts with dialysis organizations, the timing and number of generics and the pricing of generics and other products on the market that compete with Auryxia.
Added
Ferric citrate hydrate has also been approved in Japan, and is marketed and sold by our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceutical Co., Ltd., collectively, JT and Torii , as an oral treatment for the improvement of hyperphosphatemia in patients with CKD, including DD-CKD and NDD-CKD, and for the treatment of adult patients with IDA under the trade name as Riona in Japan.
Added
Averoa SAS, or Averoa , has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA , Turkey, Switzerland, the UK, the Balkans and certain countries in Eastern Europe and the Middle East. Averoa applied for marketing authorization for ferric citrate in Europe in April 2024.
Added
Our HIF-based product candidates and other pipeline assets are being evaluated to target areas of unmet needs. The discovery of HIF laid the foundation to explore the central role of oxygen sensing in many diseases.
Added
As we have seen through the development of Vafseo as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adaptive, protective responses during hypoxic or ischemic conditions.
Added
We have selected two additional HIF molecules for preclinical development: AKB-9090, potentially for cardiac surgery-related acute kidney injury, or CS-AKI , or acute respiratory distress syndrome, or ARDS , and AKB-10108 for retinopathy of prematurity, or ROP , in neonates.
Added
In June 2021, we acquired from Cyclerion Therapeutics, Inc., or Cyclerion , an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase, or sGC , stimulator. We believe there is potential to explore the use of praliciguat for indications within kidney disease.
Added
Akebia Therapeutics, Inc. | Form 10-K | Page 109 Table of Contents We continue to explore additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics through both internal research and external innovation to leverage our fully integrated team.
Added
Factors Affecting Our Performance and Results of Operations Financial Highlights Net product revenue was $152.2 million and $170.3 million for the years ended December 31, 2024 and 2023, respectively. We have incurred net losses in each year since inception. Our net losses were $69.4 million and $51.9 million for the years ended December 31, 2024 and 2023, respectively.
Added
Substantially all of our net losses resulted from costs incurred in connection with the continued commercialization of Auryxia and development and commercialization efforts relating to Vafseo, including conducting clinical trials of, and seeking regulatory approval for, Vafseo, providing general and administrative support for these operations and protecting our intellectual property.
Added
Financial Components Product Revenue We generate product revenue from commercial sales of Auryxia in the U.S. to a limited number of customers, including dialysis organizations, wholesale distributors and certain specialty pharmacy providers. Our net product revenue includes many variables, including judgments and estimates of discounts, rebates and product returns, which can fluctuate from quarter-to-quarter and year-over-year.
Added
We evaluate, at least annually and more frequently, if needed, the price of Auryxia, which will lose exclusivity in March 2025. We expect our product revenue to continue to be generated from our commercial sales of Auryxia as well as to be generated from our commercial sales of Vafseo following its U.S. market entry in January 2025.
Added
We believe the dynamics of Auryxia reimbursement being included in the end-stage renal disease, or ESRD , bundle under Medicare Part B and Auryxia LoE on March 20, 2025, could result in the buying pattern of certain customers in future years being different than their historical practices.
Added
In addition, we believe the dynamics of Auryxia reimbursement moving to Medicare Part B could result in slower revenue decline after the LoE date than in other LoE scenarios, but the impact of LoE on future Auryxia revenues will depend on many factors, including our ability to maintain contracts with dialysis organizations, the timing and number of generics and the pricing of generics and other products on the market that compete with Auryxia.
Added
License, Collaboration and Other Revenue License, collaboration and other revenue includes revenue earned under our agreements with our partners, including license fees, royalty payments and revenue from product we supply.
Added
We expect to continue to generate revenue from our collaboration, license, and supply agreements with Medice, MTPC, JT and Torii and any other collaborations into which we have entered or may enter.
Added
Cost of Goods Sold Cost of goods sold, or COGS , - Cost of product and other revenue includes costs closely correlated or directly related to the costs to manufacture commercial drug substance and drug product, including at our contract manufacturing organizations, or CMOs , as well as indirect costs.
Added
Direct and indirect costs include fees for packaging, shipping, insurance and quality assurance, idle capacity charges, changes in reserves for excess inventory, write-offs for inventory that fails to meet specifications or is otherwise no longer suitable for commercial sale, including scrap, changes in our firm purchase commitment liability and royalties due to the licensor of Auryxia related to U.S. and Japan product sales recognized during the period.
Added
COGS also includes costs to manufacture drug product provided to MTPC and Medice for commercial sale of Vafseo in Japan and the European Economic Area, or EEA , the United Kingdom, or UK , Switzerland and Australia, or the Medice Territory , respectively, as well as personnel-related costs, including salaries and bonuses, employee benefits and stock-based compensation attributable to employees in particular functions and associated directly with the manufacturing of our commercial products.
Added
Cost of product and other revenue for a newly launched product does not include the full cost of manufacturing until the initial pre-launch inventory is depleted and additional inventory is manufactured and sold.
Added
Until we received regulatory approval for Vafseo in the U.S. we recorded costs incurred to manufacture the U.S. pre-launch inventory, such as raw materials, drug substance and drug product conversion costs as research and development, or R&D , expense.
Added
Cost of goods sold - Amortization of intangible asset - In addition, COGS included the amortization of development product rights for Auryxia through the end of 2024.
Added
Akebia Therapeutics, Inc. | Form 10-K | Page 110 Table of Contents Research and Development Expenses R&D expenses consist primarily of costs incurred for the development of Vafseo prior to regulatory approval and costs associated with our pipeline which includes: • personnel-related expenses, including salaries, bonuses, employee benefits, stock-based compensation and travel expenses for employees engaged in R&D functions; • costs associated with feasibility and potential new manufacturing processes and methods for our commercial products; • regulatory registration and related fees for non-commercial products; • expenses incurred under agreements with contract research organizations, or CROs , and investigative sites that conduct our clinical trials; • the cost of acquiring, developing and manufacturing clinical trial materials through CMOs; • facilities, depreciation and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance and other supplies associated with our laboratory space as well as our R&D team; • costs associated with discovery and development for preclinical, clinical and regulatory activities; and • costs associated with the pre-launch inventory build for Vafseo in the U.S. prior to FDA approval in March 2024 and in Europe prior to the European Commission, or EC , approval in April 2023.
Added
R&D costs are expensed as incurred. Advance payments made for goods or services to be received in the future for use in R&D activities are recorded as prepaid expenses and other current assets. The prepaid amounts are expensed as the benefits are consumed.
Added
Costs for certain development activities are recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and our clinical sites.
Added
We cannot determine with certainty the duration and completion costs of our R&D projects, the costs of related clinical development, or if, when, or to what extent we will generate revenue from the commercialization or sale of any of our product candidates. From inception through December 31, 2024, we have incurred $1.7 billion in R&D expenses.
Added
We expect to incur significant R&D expenditures for the foreseeable future as we continue the development of Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired.
Added
A significant portion of our R&D costs have been external costs, which we track on a program-by-program basis as well as costs related to possible new manufacturing processes and methods associated with our commercial products.
Added
These external costs include fees paid to investigators, consultants, central laboratories and CROs in connection with our clinical trials and costs related to acquiring and manufacturing clinical trial materials, including costs paid to CMOs to manufacture clinical trial materials.
Added
We do not track our internal personnel and facilities costs on a program-by-program basis as our personnel are deployed across multiple R&D projects. Each of our products and product candidates has technical, clinical, regulatory, and commercial risk, including those discussed more fully under the heading “Risk Factors” in Part I, Item 1A of this Form 10-K.
Added
A change in the outcome of any of the variables with respect to the development of Auryxia, Vafseo or any other product or product candidate could result in a significant change in the costs and timing associated with that development.
Added
Selling, General and Administrative Expenses Selling, general and administrative, or SG&A , expenses consist primarily of compensation for personnel, including stock-based compensation related to commercial, marketing, executive, finance and accounting, information technology, corporate and business development and human resource functions.
Added
Other SG&A expenses include costs for marketing initiatives for our commercial products, market research and analysis on our commercial products and potential product candidates, conferences and trade shows, travel expenses, professional services fees (including legal, patent, accounting, audit, tax, and consulting fees), insurance costs, general corporate expenses and allocated facilities-related expenses, including rent and maintenance of facilities.
Added
License Expense License expense relates to royalties due to Panion & BF Biotech, Inc., or Panion , for sales of Auryxia in the U.S. and Riona in Japan.
Added
Other Income (Expense), Net Akebia Therapeutics, Inc. | Form 10-K | Page 111 Table of Contents Other income (expense), net consists primarily of interest income on our interest-bearing accounts, interest expense related to our term loans, accretion of the debt discount on our term loans as well as changes in the fair value of our derivative liability and amortization of the discount on the liability related to the termination fees associated with the termination agreement with BioVectra Inc., or BioVectra , entered into in December 2022, or the BioVectra Termination Agreement .
Added
See Note 10, Commitments and Contingencies, in the accompanying notes to the consolidated financial statements included in Part II, Item 8 of this Form 10-K for further information on the BioVectra Termination Agreement.
Added
Other income (expense), net also includes non-cash interest on our liability related to settlement royalties and the amortization of the discount and deferred gain related to our Working Capital Fund (as defined below) liability to Vifor (International) Ltd. (now a part of CSL Limited), or CSL Vifor .
Added
See Note 8, Liability Related to Settlement Royalties, Working Capital Fund Liability and Liability Related to Sale of Future Royalties , in the accompanying notes to the consolidated financial statements included in Part II, Item 8 of this Form 10-K for further information on our arrangements with CSL Vifor.
Added
Change in Fair Value of Warrant Liability Change in fair value of warrant liability relates to the change in fair value of our warrant liability related to a warrant agreement with Kreos Capital VII Aggregator SCSp, an affiliate of Kreos Capital VII (UK) Limited , or Kreos.
Added
See Note 3, Fair Value of Financial Instruments , and Note 7, Indebtedness , in the accompanying notes to the consolidated financial statements included in Part II, Item 8 of this Form 10-K for further information on the warrant liability.
Added
Recent Events Borrowing Under BlackRock Term Loans On February 3, 2025, we and Kreos , which are funds and accounts managed by BlackRock Inc., collectively, BlackRock , entered into the Second Amendment to the Agreement for the Provision of a Loan Facility, or the Second Amendment , which amended certain provisions of the Agreement for the Provision of a Loan Facility, dated January 29, 2024, or the BlackRock Credit Agreement .
Added
The BlackRock Credit Agreement provides for a senior secured term loan facility in the aggregate principal amount of up to $55.0 million, subject to certain customary conditions, or the Term Loan Facility .
Added
The Term Loan Facility provided us access to three tranches: (i) an initial tranche of $37.0 million, which was funded on January 29, 2024, (ii) an additional tranche of $8.0 million, which was funded on April 19, 2024, and (iii) a final tranche of $10.0 million, which was available in a single draw through an expiry date of December 31, 2024, or the Prior Tranche C Loan .
Added
As a result of the Second Amendment, the Prior Tranche C Loan expiry date was extended until February 3, 2025, or the Extended Tranche C Loan .
Added
The terms of the Extended Tranche C Loan are substantially similar to the terms of the Prior Tranche C Loan, however, interest will accrue on the Extended Tranche C Loan as if it was advanced on December 31, 2024.
Added
On February 3, 2025, we received $9.3 million on the Extended Tranche C Loan, after deducting debt issuance costs, interest, fees and expenses.
Added
On February 3, 2025, in connection with the drawdown of the Extended Tranche C Loan, in accordance with the warrant agreement, dated as of January 29, 2024, between the Company and Kreos Capital VII Aggregator SCSp, or the Warrant Holder , we issued a warrant to the Warrant Holder to purchase 1,153,846 shares of our common stock, at an exercise price per share of $1.30.
Added
The warrant shall be exercisable for eight years from the date of issuance. See Note 7, Indebtedness , and Note 18, Subsequent Events , in the accompanying notes to the consolidated financial statements included in Part II, Item 8 of this Form 10-K for further information.
Added
Cyclerion Amendment In June 2021, we entered into a license agreement, or the Cyclerion Agreement , with Cyclerion under which we obtained an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase stimulator.
Added
In December 2024, we amended the terms of the Cyclerion Agreement, pursuant to which we made an upfront payment of $1.25 million, and we will also pay Cyclerion $0.5 million on or before September 30, 2025.
Added
In addition, we and Cyclerion agreed to the reduction of certain development milestones and the increase of certain royalty rates on net sales and sublicense income. We now control all clinical and commercial manufacturing of praliciguat, which will be conducted by a third party manufacturer. We will also control patent prosecution and pay intellectual property costs starting April 1, 2025.
Added
See Note 10, Commitments and Contingencies , for further details on the Cyclerion Agreement. U.S. Approval and Commercialization of Vafseo (vadadustat) In March 2024, we received approval from the FDA for Vafseo (vadadustat) Tablets for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months.
Added
Upon Vafseo approval, we implemented a launch plan to commercialize Vafseo for the treatment of anemia due to CKD in adult patients on dialysis, the critical first step toward Vafseo potentially becoming standard of care.
Added
We have completed certain critical commercialization initiatives, including securing Akebia Therapeutics, Inc. | Form 10-K | Page 112 Table of Contents reimbursement for Vafseo under the Transitional Drug Add-on Payment Adjustment, or TDAPA , and securing access to Vafseo for patients through commercial supply agreements with dialysis organizations.
Added
The TDAPA program provides at least two years of reimbursement for Vafseo in addition to the end-stage renal disease, or ESRD , bundled rate to dialysis organizations. Additionally, we received a Level II Healthcare Common Procedure Coding System code for Vafseo which is used by dialysis organizations for billing the product for Medicare enrollees.
Added
At-the-Market (ATM) Offering On September 3, 2024, in connection with the filing of a new shelf registration statement on Form S-3, we filed a prospectus related to our amended and restated sales agreement with Jefferies LLC (which amended and restated the prior sales agreement), pursuant to which we are able to offer and sell up to $75.0 million of our common stock at current market prices from time to time.
Added
Since September 12, 2024 (the date our shelf registration statement on Form S-3 went effective) through December 31, 2024, we sold 14,271,631 shares of our common stock under this program with gross proceeds of $24.3 million ($23.8 million, net of offering expenses).

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Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeKG, or Medice , pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in patients with CKD in the EEA, the UK, Switzerland and Australia, or the Medice Territory .
Biggest changeLicense and Collaboration Agreements Vafseo License and Collaboration Agreements Medice License Agreement On May 24, 2023, or the Medice Effective Date , we entered into a License Agreement, or the Medice License Agreement , with Medice, under which we granted to Medice an exclusive license to develop and commercialize Vafseo for the treatment of anemia in adult patients with chronic kidney disease in the EEA, UK, Switzerland and Australia, or the Medice Territory .
Unless earlier terminated, the Cyclerion Agreement will expire on a product-by-product and country-by-country basis upon the expiration of the last royalty term, which ends upon the longest of (i) the expiration of the patents licensed under the Cyclerion Agreement, (ii) the expiration of regulatory exclusivity for such product and (iii) ten years from first commercial sale of such product.
Unless earlier terminated, the Cyclerion Agreement will expire on a product-by-product and country-by-country basis upon the expiration of the last royalty term, which ends upon the longest of (i) the expiration of the patents licensed under the Cyclerion Agreement, (ii) the expiration of regulatory exclusivity for such product and (iii) 10 years from first commercial sale of such product.
While seasonality may affect quarterly comparisons within a fiscal year, it generally is not material to our annual consolidated results.
While buying patterns may affect quarterly comparisons within a fiscal year, it generally is not material to our annual consolidated results.
In June 2021, we entered into a license agreement, or Cyclerion Agreement , with Cyclerion Therapeutics Inc. under which we obtained an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase stimulator.
Cyclerion Therapeutics License Agreement In June 2021, we entered into a license agreement, or the Cyclerion Agreement , with Cyclerion under which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral sGC stimulator.
Liability Related to Sale of Future Royalties In February 2021, we sold to HealthCare Royalty Partners IV L.P., or HCR , our right to receive royalties and sales milestones for vadadustat in Japan and certain other Asian countries, such countries collectively, the MTPC Territory , such payments collectively the Royalty Interest Payments , in each case, payable to us under the MTPC Agreement.
In February 2021, we entered into a royalty interest acquisition agreement with HealthCare Royalty Partners IV, L.P., or HCR , whereby we sold our right to receive royalties and sales milestones for Vafseo in Japan and certain other Asian countries in the MTPC territory under the MTPC Agreement, subject to certain caps and other terms and conditions.
We may be obligated to pay up to an aggregate of $222.0 million in specified development and regulatory milestone payments, certain specified commercial milestones and tiered royalties ranging from a low-single-digit to mid-double-digit percentage of net sales, on a product-by-product basis, and subject to reduction upon expiration of patent rights or the launch of a generic product in the territory.
Cyclerion will also be eligible to receive specified commercial milestones as well as tiered royalties ranging from a mid-single-digit percentage to twenty percent of net sales, on a product-by-product basis, and subject to reduction upon expiration of patent rights or the launch of a generic product in the territory.
As of December 31, 2023 and 2022, we had an accumulated deficit of $1.6 billion. We currently have exclusive rights under a series of patents and patent applications to commercialize Auryxia in the U.S. that protect us from generic drug competition until March 2025.
We currently have exclusive rights under a series of patents and patent applications to commercialize Auryxia in the U.S. that protect us from generic drug competition until March 20, 2025. Following LoE, in March 2025, the timing and number of generic versions of Auryxia that enter the market will affect our revenue from Auryxia.
The parties also have customary termination rights, subject to a cure period, in the event of the other party’s material breach of the Cyclerion Agreement or in the event of certain additional circumstances.
We and Cyclerion also have customary termination rights, subject to a cure period, in the event of the other party’s material breach of the Cyclerion Agreement or in the event of certain additional circumstances. Intellectual Property The proprietary nature of, and protection for, our products, product candidates and our discovery programs, processes and know-how are important to our business.
See Note 8, Deferred Revenue , Refund Liability and Liability Related to Sale of Future Royalties , in the accompanying notes to the consolidated financial statements in Part II, Item 8 of this Form 10-K for further information.
For more information on our royalty interest acquisition agreement with HCR, see Note 8, Liability Related to Settlement Royalties, Working Capital Fund Liability and Liability Related to Sale of Future Royalties , to our consolidated financial statements in Part II, Item 8. Financial Statements and Supplementary Data of this Form 10-K.
Working Capital Fund/Refund Liability In February 2022, we amended our agreement with CSL Vifor and they contributed $40.0 million to a working capital fund, or the Working Capital Fund , established to partially fund our costs of purchasing vadadustat from our contract manufacturers. The Working Capital Fund amount may fluctuate, and will be repaid to CSL Vifor over time.
Pursuant to the Vifor License Agreement, CSL Vifor contributed $40.0 million to a working capital facility, or Working Capital Fund, established to partially fund our costs of purchasing Vafseo from our contract manufacturers. On May 3, 2024, we and CSL Vifor entered into Amendment #1 to the Vifor License Agreement, or the Vifor Amendment .
License Expense License expense relates to royalties due to Panion & BF Biotech, Inc., or Panion , for sales of Auryxia in the U.S. and Riona in Japan.
During the year ended December 31, 2024, we recorded $9.1 million in royalties due to Panion relating to the sales of Auryxia in the U.S. and JT and Torii net sales of Riona in Japan.
However, we expect Auryxia to be included in the ESRD bundle starting in January 2025, which coupled with Auryxia's LoE in March 2025 may impact the buying patterns of our existing customers during 2024, and therefore their buying pattern in 2024 may be different than their historical practices.
We believe the dynamics of Auryxia reimbursement being included in the ESRD bundle under Medicare Part B and Auryxia LoE on March 20, 2025 could result in the buying pattern of certain customers in 2025 and future years being different than historical practices.
Removed
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations This Annual Report on Form 10-K, or Form 10-K , including this management's discussion and analysis of financial condition and results of operations, contains forward-looking statements based upon current expectations that involve risks and uncertainties.
Added
Item 7. Management’s Discussion and Analysis and Note 10, Commitments and Contingencies , to our consolidated financial statements in Part II, Item 8. Financial Statements and Supplementary Data. Vadadustat is a small molecule. The synthesis of vadadustat is reliable and reproducible from starting materials available from multiple sources at commercially relevant scale using no unusual manufacturing equipment.
Removed
Our actual results may differ materially from those described in or implied in these forward-looking statements as a result of various factors, including those factors set forth in the “Risk Factors” section included in Part I, Item 1A of this Form 10-K. All references to years, unless otherwise noted, refer to our fiscal years, which end on December 31.
Added
Vadadustat can be formulated into compressed tablets using proprietary processes. As with any supply program, obtaining raw materials and finished drug product of the required quality and quantity cannot be guaranteed, and we cannot ensure that we will be successful in this endeavor. Auryxia The active pharmaceutical ingredient of Auryxia, ferric citrate, is a small molecule.
Removed
For purposes of this section, all references to “we,” “us,” “our,” “Akebia,” or the “Company” refer to Akebia Therapeutics, Inc. and its consolidated subsidiaries. The following discussion and analysis should also be read in conjunction with the accompanying audited consolidated financial statements and related notes included in Part II, Item 8 of this Form 10-K.
Added
The synthesis of ferric citrate is reliable and reproducible from starting materials available from multiple sources at a commercial scale. Ferric citrate can be formulated into compressed tablets using proprietary manufacturing processes.
Removed
This section discusses 2023 and 2022 financial condition, and results of operations and year-to-year comparisons between 2023 and 2022.
Added
As with any supply program, obtaining raw materials and finished drug product of the required quality and quantity cannot be guaranteed, and we cannot ensure that we will be successful in this endeavor. We have established CMO relationships for the supply of Auryxia to help ensure that we will have sufficient material for ongoing commercial sales and clinical trials.
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For discussion of 2022 items and year-over-year comparisons between 2022 and 2021 that are not included in this 2023 Form 10-K, refer to “Item 7. – Management’s Discussion and Analysis of Financial Condition and Results of Operations” found in our Form 10-K/A for the year ended December 31, 2022, that was filed with the Securities and Exchange Commission on August 28, 2023.
Added
We currently rely on single-source suppliers for the manufacture of our drug substance and drug product for clinical and commercial supply of Auryxia. The drug substance for Auryxia is supplied by Siegfried Evionnaz SA, or Siegfried , pursuant to a supply agreement, as amended, with pricing structured on a per-kilogram ba sis.
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Business Overview We are a fully integrated commercial-stage biopharmaceutical company committed to addressing patients’ unmet needs. We have built a business focused on developing and commercializing innovative therapeutics that we believe serves as a foundation for future growth.
Added
A uryxia drug product is supplied by Patheon Manufacturing Services LLC (Thermo Fisher) pursuant to a Master Manufacturing Service Agreement with per-bottle pricing structured on a tiered basis, with the price reduced as the product volume increases.
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Our purpose is to better the life of each person impacted by kidney disease, and we have established ourselves as a leader in the kidney community. We believe our demonstrated ability to deliver value broadly to the kidney community has enabled us to build a sustainable company.
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The supply agreement with Siegfried requires that we satisfy certain minimum purchase requirements, but we are not obligated to use Siegfried as our exclusive supplier. For more information about our manufacturing agreements for Auryxia, see Part II, Item 7. Management’s Discussion and Analysis and Note 10, Commitments and Contingencies , to our consolidated financial statements in Part II, Item 8.
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Upon this solid foundation and our continued Akebia Therapeutics, Inc. | Form 10-K | Page 110 Table of Content s commitment to patients, we believe focusing on all patients who can realize a meaningful benefit from our medicines, will result in delivering value for our shareholders.
Added
Financial Statements and Supplementary Data. We utilize third parties for the commercial distribution of Auryxia, including wholesale distributors and certain specialty pharmacy providers. We have also engaged Cardinal Health, Inc., as the exclusive third-party logistics distribution agent for commercial sales of Auryxia and Vafseo.
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Our current portfolio includes: • Auryxia® (ferric citrate) is an an orally administered medicine approved and marketed in the United States, or U.S. , for two indications: (1) the control of serum phosphorus levels in adult patients with dialysis dependent chronic kidney disease, or DD-CKD , and (2) the treatment of iron deficiency anemia, or IDA , in adult patients with non-dialysis-dependent chronic kidney disease, or NDD-CKD .
Added
The third-party logistics provides services to the Company that include storage, distribution, processing product returns, customer service support, logistics support, electronic data interface and system access support.
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Today, we market Auryxia in the U.S. with our well-established, nephrology-focused commercial organization. Our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceutical Co., Ltd., collectively, JT and Torii , commercialize ferric citrate hydrate as Riona in Japan.
Added
Under the Medice License Agreement, we received an up-front payment of $10.0 million and are eligible to receive the following payments: (i) commercial milestone payments up to an aggregate of $100.0 million, and (ii) tiered royalties ranging from 10% to 30% of Medice's annual net sales of Vafseo in the Medice Territory, subject to reduction in certain circumstances.
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Averoa SAS, or Averoa , has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA , Turkey, Switzerland and the United Kingdom, or UK .
Added
The royalties will expire on a country-by-country basis upon the latest to occur of (i) the date of expiration of the last-to-expire valid claim of ours, Medice or joint patent that covers Vafseo in such country in the Medice Territory, (ii) the date of expiration of data or regulatory exclusivity for Vafseo in such country in the Medice Territory and (iii) the date that is 12 years from first commercial sale of Vafseo in such country in the Medice Territory.
Removed
We expect Averoa will apply for marketing authorization for ferric citrate in Europe. • Vafseo™ (vadadustat) is an oral hypoxia-inducible factor prolyl hydroxylase, or HIF-PH , inhibitor, approved in 36 countries as a treatment for anemia due to CKD.
Added
Under the Medice License Agreement, we retain the right to develop Vafseo for non-dialysis patients with anemia due to CKD in the Medice Territory. If we develop Vafseo for non-dialysis patients and Vafseo receives marketing approval for non-dialysis patients in the Medice Territory, Medice will commercialize Vafseo for both indications in the Medice Territory.
Removed
In the European Union, or EU , the UK, Switzerland and Australia, vadadustat is approved under the trade name Vafseo for the treatment of symptomatic anemia associated with chronic kidney disease, or CKD , in adults on chronic maintenance dialysis. In May 2023, we entered into a License Agreement with MEDICE Arzneimittel Pütter GmbH & Co.
Added
In this instance, we would receive 70% of the net product margin of any sales of Vafseo in the non-dialysis patient population, unless Medice requests to share the cost of the development necessary to gain approval to market Vafseo for non-dialysis patients in the Medice Territory and the parties agree on alternative financial terms.
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In Japan, vadadustat is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent patients under the trade name Vafseo, and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporation, or MTPC .
Added
We and Medice established a joint steering committee to oversee the development and commercialization of Vafseo in the Medice Territory.
Removed
In Taiwan, vadadustat is approved for the treatment of symptomatic anemia due to CKD in adult patients on chronic maintenance dialysis and in Korea as an anemia treatment for patients with CKD on hemodialysis. MTPC plans to commercialize vadadustat in Taiwan.
Added
Akebia Therapeutics, Inc. | Form 10-K | Page 15 Table of Contents The Medice License Agreement expires on the date of expiration of all payment obligations due thereunder with respect to Vafseo in the last country in the Medice Territory, unless earlier terminated in accordance with the terms of the Medice License Agreement.
Removed
We continue to pursue approval for vadadustat in the U.S., and in September 2023, we completed our resubmission to our New Drug Application, or NDA , for the treatment of anemia due to CKD for dialysis dependent patients to the U.S. Food and Drug Administration, or FDA .
Added
Either party may, subject to a cure period, terminate the Medice License Agreement in the event of the other party's uncured material breach. Medice has the right to terminate the Medice License Agreement in its entirety for convenience upon twelve months' prior written notice delivered on or after the date that is twelve months after the Medice Effective Date.
Removed
In October 2023, the FDA acknowledged that the resubmission was complete, classified it as a Class 2 response and set a user fee goal date, or PDUFA Date , of March 27, 2024.
Added
The Medice License Agreement includes customary terms relating to, among others, indemnification, confidentiality, remedies, and representations and warranties. On September 13, 2024, we entered into a supply agreement, or the Medice Supply Agreement , with Medice under which we supply Vafseo drug product to Medice for commercial and developmental use in the Medice Territory.
Removed
Beyond seeking U.S. approval, we have several lifecycle management and indication expansion opportunities currently under evaluation for vadadustat, including the potential for alternative dosing and label expansion for treatment of adult patients not on dialysis. • Our HIF-based pipeline assets are molecules being evaluated to target areas of unmet needs in acute care settings.
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MTPC Collaboration Agreement In December 2015, we entered into a collaboration agreement with MTPC, as amended, or the MTPC Agreement , providing MTPC with exclusive development and commercialization rights to Vafseo in Japan and certain other Asian countries, or the MTPC Territory .
Removed
The discovery of hypoxia-inducible factor, or HIF , laid the foundation to explore the central role of oxygen sensing in many diseases. As we have seen through the development of vadadustat as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adaptive, protective responses during hypoxic or ischemic conditions.
Added
In addition, we supply Vafseo to MTPC for both clinical and commercial use in the MTPC Territory, subject to MTPC’s option to manufacture commercial drug product in the MTPC Territory.
Removed
We have selected two additional HIF molecules for preclinical development: AKB-9090, for use in an acute care setting, potentially for acute kidney disease, or AKI , or acute respiratory distress syndrome, or ARDS , and AKB-10108 for retinopathy of prematurity, or ROP , in neonates.
Added
On July 15, 2020, we entered into a supply agreement with MTPC for the commercial supply of Vafseo for use in Japan and certain other Asian countries, as contemplated by the MTPC Agreement, which was amended effective as of December 5, 2022.
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We continue to explore additional commercial and development opportunities to expand our pipeline and portfolio of novel therapeutics through both internal research and external innovation to leverage our fully integrated team.
Added
Unless earlier terminated, the MTPC Agreement will continue in effect on a country-by-country basis until the later of the following: (i) expiration of the last-to-expire patent covering Vafseo in such country in the MTPC Territory; (ii) expiration of marketing or regulatory exclusivity in such country in the MTPC Territory; or (iii) ten years after the first commercial sale of Vafseo in such country in the MTPC Territory.
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Factors Affecting Our Performance and Results of Operation Financial Highlights Net product revenue in 2023 decreased by approximately 4% to $170.3 million from $176.9 million in 2022, primarily due to a decrease in Auryxia product volume partially offset by increases in pricing, improved payor mix and execution of our contracting strategy with third-party payors.
Added
MTPC may terminate the MTPC Agreement upon twelve months’ notice. Either party may terminate the MTPC Agreement upon the material breach of the other party that is not cured within a specified time period or upon the insolvency of the other party.
Removed
We have incurred net losses in each year since inception. Our net losses were $51.9 million and $94.2 million for the years ended December 31, 2023 and 2022, respectively.
Added
Under the terms of the MTPC Agreement, we are eligible to receive payments from MTPC of up to approximately $225.0 million in the aggregate based on the achievement of certain development, regulatory and sales milestones, as well as tiered royalty payments ranging from 13% to 20% on annual net sales of Vafseo in the MTPC Territory, subject to reduction upon launch of a generic product on a country-by-country basis.
Removed
Substantially all of our net losses resulted from costs incurred in connection with the continued commercialization of Auryxia and development efforts relating to vadadustat, including conducting clinical trials of, and seeking regulatory approval for, vadadustat, providing general and administrative support for these operations and protecting our intellectual property.
Added
CSL Vifor License Agreement On February 18, 2022, we entered into a Second Amended and Restated License Agreement, or the Vifor License Agreement , with Vifor (International) Ltd. (now a part of CSL Limited), or CSL Vifor, which amended and restated the License Agreement dated as of May 12, 2017.
Removed
Financial Components Product Revenue We generate product revenue from commercial sales of Auryxia to a limited number of wholesale distributors as well as certain specialty pharmacy providers. Our net product revenue includes many variables, including judgments and estimates of discounts, rebates and product returns, which can fluctuate from quarter-to-quarter and year-over-year.
Added
The Vifor License Agreement granted CSL Vifor an exclusive license to sell Vafseo to Fresenius Medical Care North America and its affiliates, including Fresenius Kidney Care Group LLC, to certain third-party dialysis organizations approved by us, to independent dialysis organizations that are members of certain group purchasing organizations and certain non-retail specialty pharmacies, collectively, the Supply Group , in the U.S.
Removed
We evaluate, at least Akebia Therapeutics, Inc. | Form 10-K | Page 111 Table of Content s annually and more frequently, if needed, the price of Auryxia, which will lose exclusivity, or LoE , in March 2025. We expect our product revenue to continue to be generated primarily from our commercial sales of Auryxia.
Added
The Vifor License Agreement was structured as a profit share arrangement between us and CSL Vifor in which we would receive approximately 66% of the profits, net of certain pre-specified costs. CSL Vifor made an upfront payment to us of $25.0 million in February 2022 in connection with the amendment and restatement of the Vifor License Agreement.
Removed
Due to the buying patterns of our customers we tend to have seasonality from quarter to quarter. In general, our first quarter usually has lower revenues than the preceding fourth quarter, the second and third quarters have higher revenues than the first quarter, and the fourth quarter revenues are the highest in the year.
Added
In addition, we entered into certain investment agreements with CSL Vifor, pursuant to which we sold CSL Vifor an aggregate of 7,571,429 shares of our common stock for a total of $70.0 million.
Removed
We believe the Centers for Medicare & Medicaid Services', or CMS , decision to include phosphate binders in the dialysis bundle could potentially lead to higher sales of Auryxia after the LoE date than in other LoE scenarios, and plan to work with payors and providers to seek to continue the use of Auryxia beyond LoE.
Added
The shares have not been registered pursuant to the Securities Act of 1933, as amended, or the Securities Act, and were issued and sold in reliance upon the exemption from registration contained in Section 4(a)(2) of the Securities Act and Rule 506 promulgated thereunder as the transaction did not involve any public offering within the meaning of Section 4(a)(2) of the Securities Act.
Removed
License, Collaboration and Other Revenue License, collaboration and other revenue includes revenue earned under collaboration agreements, license fees, royalty payments and revenue from product we supply under our license and supply agreements with our collaboration partners.
Added
On July 10, 2024, we and CSL Vifor entered into the Vifor Termination and Settlement Agreement, or the Vifor Termination Agreement , pursuant to which we and CSL Vifor agreed, among other things, to terminate, effective immediately, the Vifor License Agreement.
Removed
We expect to continue to generate revenue from our collaboration and, if applicable, supply agreements with Medice, MTPC, JT and Torii and any other collaborations into which we have entered or may enter, including our collaboration with Vifor (International) Ltd. (now a part of CSL Limited), or CSL Vifor, if vadadustat is approved in the U.S.
Added
Pursuant to the terms of the Vifor Termination Agreement, we will pay CSL Vifor decreasing quarterly tiered royalty payments ranging from a high single-digit percentage of our net sales of Vafseo up to $450.0 million to mid-single digit percentage of Akebia Therapeutics, Inc. | Form 10-K | Page 16 Table of Contents our net sales of Vafseo above $450.0 million, in each case, in the U.S. during a calendar year, or the Settlement Royalty Payments .
Removed
In 2022, we recorded a nonrefundable, non-creditable termination fee pursuant to the terms of the Termination and Settlement Agreement, or Termination Agreement , with Otsuka Pharmaceutical Co. Ltd, or Otsuka. Furthermore, in 2023 we recorded a payment received from Otsuka, in connection with the Packaging Validation Transfer Agreement, to license, collaboration and other revenue.
Added
The Settlement Royalty Payments will commence upon the first sale of Vafseo by us, our affiliates or third-party licensees to a third party for use in the U.S., and will continue until the later of the (i) expiration of the last-to-expire valid claim listed in the FDA Orange Book that would be infringed by the making, using, selling or importing of Vafseo in the U.S. or (ii) the expiration of marketing or regulatory exclusivity for Vafseo in the U.S., or the Settlement Royalty Term .
Removed
Also in 2022, we recorded revenue from cost sharing agreements under which we were reimbursed by our collaboration partner for expenses incurred by us for research and development, or R&D , activities and, may in the future generate revenue from potential co-promotion activities, under our collaboration agreements.
Added
Beginning on July 1, 2027 and throughout the Settlement Royalty Term, we have the option to make a one-time payment to CSL Vifor, or the Royalty Buy-Down Option , upon which the Settlement Royalty Payments will be adjusted as of the date of exercise of the Royalty Buy-Down Option such that we will then only pay CSL Vifor quarterly royalty payments based on a mid-single digit percentage of our net sales of Vafseo up to $450.0 million in the U.S. during a calendar year in lieu of the above Settlement Royalty Payments.
Removed
We do not expect to recognize any future revenue under any of our collaboration agreements with Otsuka, which were terminated on June 30, 2022.
Added
If we exercise the Royalty Buy-Down Option, the WCF Royalty Payments, as described below, will continue.
Removed
Cost of Goods Sold Cost of goods sold, or COGS , - Cost of product and other revenue - COGS - Cost of product and other revenue includes costs closely correlated or directly related to the costs to manufacture commercial drug substance and drug product for Auryxia, including at our contract manufacturing organizations, or CMOs , as well as indirect costs.
Added
The WCF Royalty Payments, as described below, the Settlement Royalty Payments and the Royalty Buy-Down Option are in consideration for the termination of the Vifor License Agreement and all obligations thereunder, and the covenants and agreements set forth in the Vifor Termination Agreement, including the settlement and release of all disputes and claims which could arise from the Vifor License Agreement.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeItem 7A. Quantitative and Qualitative Disclosures about Market Risk We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act, and are not required to provide information under this item. Akebia Therapeutics, Inc. | Form 10-K | Page 124 Table of Content s
Biggest changeItem 7A. Quantitative and Qualitative Disclosures about Market Risk We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act, and are not required to provide information under this item. Akebia Therapeutics, Inc. | Form 10-K | Page 122 Table of Contents

Other AKBA 10-K year-over-year comparisons