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What changed in AMARIN CORP PLCUK's 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of AMARIN CORP PLCUK's 2022 and 2023 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 2023 report.

+655 added−769 removedSource: 10-K (2024-02-29) vs 10-K (2023-03-01)

Top changes in AMARIN CORP PLCUK's 2023 10-K

655 paragraphs added · 769 removed · 493 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

145 edited+54 added−119 removed188 unchanged
Biggest changeBased on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, 30 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2022 as listed below: • In November 2022, the American Society of Preventive Cardiology published a clinical practice statement delineating key attributes that define the field of preventive cardiology, including that REDUCE-IT established that icosapent ethyl, or IPE, reduced CV events among patients fasting TG 135 to 499 mg/dL and that results from REDUCE-IT have not been replicated in trials using mixed omega-3 fatty acids suggesting that the CV benefit is attributed to EPA. • In November 2022, NICE released its guidelines on lipid management, which included that IPE is recommended for patients with established CVD and elevated fasting TG and who are taking statins with LDL-C levels between 1.04 and 2.60 mmol/L, as per the REDUCE-IT results. 6 • In December 2022, the Finnish Medical Association and the Finnish Association of Internists published updated guidelines on dyslipidemia treatment, including that IPE is indicated for patients on statin therapy who have elevated TG levels and are at particularly high risk for arterial disease. • In December 2022, the National Society of Cardiometabolic Medicine in China released its consensus statement on the role of omega-3 fatty acids in the prevention and treatment of CVD in Chinese patients.
Biggest changeBased on REDUCE-IT results, as of the date of the filing of this Annual Report, more than 40 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2023 as listed below: • In December 2023, the Hellenic Atherosclerosis Society published guidelines for the diagnosis and treatment of dyslipidemia.
All findings from these studies were consistent with our expectations and confirmed the overall safety profile of VASCEPA. Clinical Study in China Edding completed a Phase 3 study of VASCEPA in China, the study design of which was similar to, but larger than, our MARINE study. In November 2020, along with Edding, we announced statistically significant topline positive results.
All findings from these studies were consistent with our expectations and confirmed the overall safety profile of VASCEPA. Clinical Study in China Edding completed a Phase 3 study of VASCEPA in China, the design of which was similar to, but larger than, our MARINE study. In November 2020, along with Edding, we announced statistically significant topline positive results.
Also, if governmental parties or our competitors view our claims as misleading or false, we could also be subject to liability based on fair competition-based statutes, such as the Lanham Act. Any of such negative circumstances could adversely affect our ability to operate our business and our results of operations.
Also, if governmental parties or our competitors view our claims as misleading or false, we could also be subject to liability based on fair competition-based statutes, such as the Lanham Act. Any of such negative circumstances could adversely affect our ability to operate our business and our results of operations.
Price negotiations are conducted in each EU (and UK) country for new medicines between the manufacturer and the national government pricing committee, or the parties. In many cases, there is no specific timeline for negotiation conclusion and the dynamics depends on the discussions between both parties.
Price negotiations are conducted in the UK and each EU country for new medicines between the manufacturer and the national government pricing committee, or the parties. In many cases, there is no specific timeline for negotiation conclusion and the dynamics depends on the discussions between both parties.
Recently, real world administrative database analyses have reported an increased CVD risk as well as direct healthcare costs associated with HTG despite statin therapy and controlled LDL-C compared to those with TG Regulatory Matters Government Regulation and Regulatory Matters Any product development activities related to VASCEPA or products that we may develop or acquire in the future will be subject to extensive regulation by various government authorities, including the U.S.
Recently, real world administrative database analyses have 11 reported an increased CVD risk as well as direct healthcare costs associated with HTG despite statin therapy and controlled LDL-C compared to those with TG Regulatory Matters Government Regulation and Regulatory Matters Any product development activities related to VASCEPA or products that we may develop or acquire in the future will be subject to extensive regulation by various government authorities, including the U.S.
Our commercialized product, VASCEPA ® (icosapent ethyl) was first approved by the United States, or U.S., Food and Drug Administration, or U.S. FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication, and commercially launched in 2013. On December 13, 2019, the U.S.
Our commercialized product, VASCEPA ® (icosapent ethyl) was first approved by the United States, or U.S., Food and Drug Administration, or U.S. FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication and we commercially launched in 2013. On December 13, 2019, the U.S.
Treating LDL-C remains an important secondary goal. Other important parameters to consider in patients with very high triglycerides include levels of apolipoprotein B, or apo B, non-HDL-C, and very low-density lipoprotein cholesterol, or VLDL-C. The effect of VASCEPA on the risk for pancreatitis in patients with hypertriglyceridemia has not been determined.
Treating LDL-C remains an important secondary goal. 8 Other important parameters to consider in patients with very high triglycerides include levels of apolipoprotein B, or apo B, non-HDL-C, and very low-density lipoprotein cholesterol, or VLDL-C. The effect of VASCEPA on the risk for pancreatitis in patients with hypertriglyceridemia has not been determined.
FDA and IRB, respectively. Once the CTA is approved in accordance with a country’s requirements, clinical trial development may proceed. Similarly, clinical trials conducted in countries such as Australia, Canada, and New Zealand, require review and approval of clinical trial proposals by an ethics committee, which provides a combined ethical and scientific review process.
FDA and IRB, respectively. Once the CTA is approved in accordance with a country’s requirements, clinical trial development may proceed. Similarly, clinical trials conducted in countries such as Australia, Canada, and New Zealand, require review and approval of clinical trial proposals by an ethics committee, 14 which provides a combined ethical and scientific review process.
Accordingly, we expect to receive three-year exclusivity in connection with any future regulatory approvals of VASCEPA. For example, we received such three-year regulatory exclusivity in connection with the approval based on the REDUCE-IT outcomes study results. Such three-year exclusivity protection precludes the U.S. FDA from approving a marketing application for an ANDA, a product candidate that the U.S.
Accordingly, we expect to receive three-year exclusivity in connection with any future regulatory approvals of VASCEPA. We received such three-year regulatory exclusivity in connection with the approval based on the REDUCE-IT outcomes study results. Such three-year exclusivity protection precludes the U.S. FDA from approving a marketing application for an ANDA, a product candidate that the U.S.
Item 1. B usiness References in this Annual Report on Form 10-K to “Amarin,” the “Company,” “we,” “our” and “us” refer to Amarin Corporation plc and its subsidiaries, on a consolidated basis, unless otherwise indicated. This Annual Report on Form 10-K includes the registered and unregistered trademarks and service marks of other parties.
Item 1. B usiness References in this Annual Report on Form 10-K to “Amarin,” the “Company,” “we,” “our” and “us” refer to Amarin Corporation plc and its subsidiaries, on a consolidated basis, unless otherwise indicated. This Annual Report on Form 10-K, or Annual Report, includes the registered and unregistered trademarks and service marks of other parties.
Employee Development & Engagement We believe in a direct management-employee engagement model by which managers and employees maintain a regular dialogue about working conditions, compensation, compliance, safety and advancement opportunities. We communicate frequently and transparently with our employees through a variety of communication methods, including written communications and quarterly town hall meetings.
Employee Development & Engagement We believe in a direct management-employee engagement model by which managers and employees maintain a regular dialogue about working conditions, compensation, compliance, safety and advancement opportunities. We communicate frequently and transparently with our employees through a variety of communication methods, including written and video communications and quarterly town hall meetings.
There is currently no other drug that is approved for cardiovascular risk reduction in at-risk patients in Europe. In addition, there is currently no other direct competition for Canada and the Middle East. However, consistent with the U.S., our competitors include large, well-established pharmaceutical companies, specialty and generic pharmaceutical companies, marketing companies, and specialized cardiovascular treatment companies.
There is currently no other drug that is approved for cardiovascular risk reduction in at-risk patients in Europe. In addition, there is currently no other direct competition for Canada and the Middle East. However, consistent with the U.S., our competitors globally include large, well-established pharmaceutical companies, specialty and generic pharmaceutical companies, marketing companies, and specialized cardiovascular treatment companies.
In addition to the REDUCE-IT, MARINE and ANCHOR trials, we completed a 28-day pharmacokinetic study in healthy volunteers, a 26-week study to evaluate the toxicity of VASCEPA in transgenic mice and multiple pharmacokinetic drug-drug interaction studies in healthy subjects in which we evaluated the effect of VASCEPA on certain common prescription drugs.
In addition to the REDUCE-IT, MARINE and ANCHOR trials, we completed a 28-day pharmacokinetic study in healthy volunteers, a 26-week study to evaluate the toxicity of VASCEPA in transgenic mice and multiple pharmacokinetic drug-drug 7 interaction studies in healthy subjects in which we evaluated the effect of VASCEPA on certain common prescription drugs.
Attracting, developing and retaining key scientific, technical, research, marketing, sales and other personnel is critical to our ability to implement and execute our business plan and is key to the success of the business. Our ability to recruit and retain such talent depends on a number of factors, including compensation and benefits, talent development, career opportunities and work environment.
Attracting, developing and retaining key scientific, technical, research, marketing, sales and other personnel is critical to our ability to implement and execute our business plan and is key to our success. Our ability to recruit and retain such talent depends on a number of factors, including compensation and benefits, talent development, career opportunities and work environment.
An independent IRB may also suspend or terminate a study once initiated. U.S. FDA Review Process The results of nonclinical studies and clinical trials, together with other information, including manufacturing information and information on the composition of the drug and proposed labeling, are submitted to the U.S.
An independent IRB may also suspend or terminate a study once initiated. 12 U.S. FDA Review Process The results of nonclinical studies and clinical trials, together with other information, including manufacturing information and information on the composition of the drug and proposed labeling, are submitted to the U.S.
Our ability to successfully commercialize our product therefore depends significantly on the availability of adequate financial coverage and reimbursement from third-party payors, including, in the United States, governmental payors such as Medicare and Medicaid, as 21 well as managed care organizations, private health insurers and other organizations.
Our ability to successfully commercialize our product therefore depends significantly on the availability of adequate financial coverage and reimbursement from third-party payors, including, in the United States, governmental payors such as Medicare and Medicaid, as well as managed care organizations, private health insurers and other organizations.
Furthermore, patent protection in Europe includes: one allowed patent related to the use of a pharmaceutical composition comprised of 4g of 96% EPA ethyl ester to treat the REDUCE-IT population expiring 2033. In addition, pending patent applications in Europe, if granted, may have the potential to extend exclusivity into 2039.
Furthermore, patent protection in Europe includes: one granted patent related to the use of a pharmaceutical composition comprised of 4g of 96% EPA ethyl ester to treat the REDUCE-IT population expiring 2033. In addition, pending patent applications in Europe, if granted, may have the potential to extend exclusivity into 2039.
United States VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients and healthcare providers.
United States VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and retail and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients.
Any authorization that is not followed by the placement of the product on the EU market, in the 15 case of the centralized procedure, or on the market of the authorizing Member State for a nationally authorized product, within three years after authorization, or if the product is removed from the market for three consecutive years, ceases to be valid.
Any authorization that is not followed by the placement of the product on the EU market, in the case of the centralized procedure, or on the market of the authorizing Member State for a nationally authorized product, within three years after authorization, or if the product is removed from the market for three consecutive years, ceases to be valid.
On June 28, 18 2021, the EC adopted an adequacy decision in respect of transfers of personal data to the UK for a four year period until June 27, 2025. Similarly, the UK has determined that it considers all of the EEA to be adequate for the purposes of data protection.
On June 28, 2021, the EC adopted an adequacy decision in respect of transfers of personal data to the UK for a four year period until June 27, 2025. Similarly, the UK has determined that it considers all of the EEA to be adequate for the purposes of data protection.
While certain key patents related to our product based on the MARINE clinical study were determined to be invalid as obvious by a district court in the United States, it remains the case that our ability to successfully implement our business plan and to protect our products with our intellectual property will depend in large part on our ability to: • obtain, defend and maintain patent protection and market exclusivity for our current and future products; • preserve any trade secrets relating to our current and future products; 25 • acquire patented or patentable products and technologies; and • operate without infringing the proprietary rights of third parties.
While certain key patents related to our product based on the MARINE clinical study were determined to be invalid as obvious by a district court in the United States, it 22 remains the case that our ability to successfully implement our business plan and to protect our products with our intellectual property will depend in large part on our ability to: • obtain, defend and maintain patent protection and market exclusivity for our current and future products; • preserve any trade secrets relating to our current and future products; • acquire patented or patentable products and technologies; and • operate without infringing the proprietary rights of third parties.
We are responsible for the supply of VASCEPA to all markets in which the branded product is sold, either directly by us or to and through our collaborations with third-party companies. We are not responsible for providing any generic company with drug product.
We are responsible for the supply of VASCEPA to all markets in which the branded product is sold, either to and through our collaborations with third-party companies or by us. We are not responsible for providing any generic company with drug product.
For example, the new Regulation provides for a streamlined application procedure through a single entry point and strictly defined deadlines for the assessment of clinical trial applications. Drug Review and Approval Medicinal products can only be commercialized after obtaining a marketing authorization.
For example, the Regulation provides for a streamlined application procedure through a single entry point and strictly defined deadlines for the assessment of clinical trial applications. Drug Review and Approval Medicinal products can only be commercialized after obtaining a marketing authorization.
The regulatory process generally requires extensive details as part of the submission provided to a country or region in connection with a company's request for regulatory approval. Suppliers must be specifically identified as part of the submission for 9 qualification and approval for commercialization in a country or region.
The regulatory process generally requires extensive details as part of the submission provided to a country or region in connection with a company's request for regulatory approval. Suppliers must be specifically identified as part of the submission for qualification and approval for commercialization in a country or region.
Over 1,000 patients 7 were dosed with VASCEPA in these studies, with over 100 receiving continuous treatment for a year or more. In all studies performed to date, VASCEPA has shown a favorable safety and tolerability profile.
Over 1,000 patients were dosed with VASCEPA in these studies, with over 100 receiving continuous treatment for a year or more. In all studies performed to date, VASCEPA has shown a favorable safety and tolerability profile.
The MHRA also has the power to have regard to marketing authorizations approved in EU Member States through decentralized or mutual recognition procedures with a view to more quickly granting a marketing authorization in the UK or Great Britain.
The MHRA also has the power to have regard to marketing authorizations approved in 15 EU Member States through decentralized or mutual recognition procedures with a view to more quickly granting a marketing authorization in the UK or Great Britain.
We utilize independent consultants to help us ensure that 27 our compensation and benefits are competitive with market practices and compliant with laws and regulations in the various geographies in which we operate.
We utilize independent consultants to help us ensure that our compensation and benefits are competitive with market practices and compliant with laws and regulations in the various geographies in which we operate.
As summarized from the primary results of REDUCE-IT in The New England Journal of Medicine, potential VASCEPA mechanisms of action at work in REDUCE-IT may include TG reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/or regression of coronary plaque and inflammation reduction, each as supported by earlier stage mechanistic studies. The U.S.
As summarized from the primary results of REDUCE-IT in The New England Journal of Medicine, potential VASCEPA mechanisms of action at work in REDUCE-IT may include TG reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/or regression of coronary plaque and inflammation reduction, each as supported by earlier stage mechanistic studies.
The federal Physician Payment Sunshine Act, implemented as the Open Payments Program, requires manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to direct or indirect payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.
The federal Physician Payment Sunshine Act, implemented as the Open Payments Program, requires manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the Centers for Medicare and Medicaid Services, or CMS, information related to direct or indirect payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other licensed healthcare practitioners and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.
The UK has announced plans to reform the country’s data protection legal framework in its Data Reform Bill, which will introduce significant changes from the GDPR.
The UK has announced plans to reform the country’s data protection legal framework in its Data Reform Bill, which will introduce significant changes from the EU GDPR.
In addition, other technologies or products may be developed that have an entirely different approach or means of accomplishing the intended purposes of our products, which might render our technology and products noncompetitive or obsolete. United States Our competitors include large, well-established pharmaceutical and generic companies, specialty and generic pharmaceutical sales and marketing companies, and specialized cardiovascular treatment companies.
In addition, other technologies or products may be developed that have an entirely different approach or means of accomplishing the intended purposes of our products, which might render our technology and products noncompetitive or obsolete. United States Our competitors include large, well-established pharmaceutical and generic companies, specialty and generic pharmaceutical companies, and specialized cardiovascular treatment companies.
Production of VASCEPA, from sourcing of starting materials through stocking of finished goods inventory requires significant coordination between companies and considerable lead-times. We are often making purchasing decisions for supply more than a year in advance of anticipated product sales.
Production of VASCEPA, from sourcing of raw materials through stocking of finished goods inventory requires significant coordination between companies and considerable lead-times. We are often making purchasing decisions for supply more than a year in advance of anticipated product sales.
FDA-approved products for uses that have not been approved by the U.S. FDA. Companies that market drugs for off-label uses or indications have been subject to related costly litigation, criminal penalties and civil liability under the FDCA and the False Claims Act.
FDA-approved products for uses that have not been approved by the U.S. FDA, or off-label promotion. Companies that market drugs for unapproved uses or indications have been subject to related costly litigation, criminal penalties and civil liability under the FDCA and the False Claims Act.
REDUCE-IT met its primary endpoint demonstrating a 25% RRR, to a high degree of statistical significance (p VASCEPA in the REDUCE-IT study demonstrated a number needed to treat, or NNT, of 21 for the first occurrence of MACE in the 5-point primary composite endpoint.
REDUCE-IT met its primary endpoint demonstrating a 25% RRR, to a high degree of statistical significance (p VASCEPA in the REDUCE-IT study demonstrated a number needed to treat, or NNT, of 21 for the first occurrence of MACE in the five-point primary composite endpoint.
FDA typically inspects manufacturing facilities before regulatory approval of a product candidate, such as VASCEPA, and on a periodic basis after the initial approval. Consistent with cGMP regulations, pharmaceutical manufacturers must expend resources and time to ensure compliance with product specifications as well as production, record keeping, quality control, reporting, and other regulatory requirements. Similar to the U.S.
FDA typically inspects manufacturing facilities before regulatory approval of a product candidate, such as VASCEPA, and on a periodic basis after the initial approval. Consistent with cGMP regulations, pharmaceutical manufacturers must expend resources and time to ensure compliance with product specifications as well as production, record keeping, quality control, reporting, and other regulatory requirements.
Diversity and Inclusion We believe that a diverse and inclusive workforce helps us better connect our work with the needs of our patients, physicians, partners and other stakeholders. In our hiring and recruiting of prospective candidates, we give priority to attitude, intelligence, competency for the position and assessment of what they can contribute to our company.
Human Capital Management Diversity and Inclusion We believe that a diverse and inclusive workforce helps us better connect our work with the needs of our patients, physicians, partners and other stakeholders. In our hiring and recruiting of prospective candidates, we give priority to attitude, intelligence, competency for the position and assessment of what they can contribute to our company.
The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.
The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million (£17.5 million for the UK GDPR) or 4% of annual global revenues, whichever is greater.
This ensures that data flows between the UK and the EEA remain unaffected. Despite Brexit, the GDPR and UK GDPR remain largely aligned. Currently, the most impactful point of divergence between the GDPR and the UK GDPR relates to these transfer mechanisms as explained above. There may be further divergence in the future, including with regard to administrative burdens.
This ensures that data flows between the UK and the EEA remain unaffected. The EU GDPR and UK GDPR remain largely aligned. Currently, the most impactful point of divergence between the GDPR and the UK GDPR relates to these transfer mechanisms as explained above. There may be further divergence in the future, including with regard to administrative burdens.
For purposes of this Annual Report on Form 10-K, our ordinary shares may also be referred to as “common shares” or “common stock.” Overview We are a pharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular, or CV, health and reduce CV risk.
For purposes of this Annual Report, our ordinary shares may also be referred to as “common shares” or “common stock.” Overview We are a pharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular, or CV, health and reduce CV risk.
These rules can impose post-authorization studies and additional monitoring obligations. • The manufacturing of authorized medicinal products, for which a separate manufacturer's license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive 2003/94/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines Manufacturing Practice.
These rules can impose post-authorization studies and additional monitoring obligations. • The manufacturing of authorized medicinal products, for which a separate manufacturer's license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive (EU) 2017/1572, Regulation (EC) No 726/2004 and the European Commission Guidelines Manufacturing Practice.
The MARINE Trial (first U.S. FDA-approved label for VASCEPA approved in July 2012) The MARINE trial was a Phase 3, multi-center, placebo-controlled, randomized, double-blind, 12-week study for patients with very high triglycerides which was completed in 2010. In November 2010, we reported topline data for the MARINE trial.
FDA-approved label for VASCEPA approved in July 2012) The MARINE trial was a Phase 3, multi-center, placebo-controlled, randomized, double-blind, 12-week study for patients with very high triglycerides which was completed in 2010. In November 2010, we reported topline data for the MARINE trial.
State and foreign laws, including for example the California Consumer Privacy Act, or CCPA, and the European Union General Data Protection Regulation, or GDPR, also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
State and foreign laws, including for example the California Consumer Privacy Act, or CCPA, and the European Union General Data Protection Regulation, or EU GDPR, and the UK equivalent of the same, or the UK GDPR, also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Biologix obtained approval of VASCEPA under the MARINE and REDUCE-IT indications, and subsequently launched commercially in the following countries: Country MARINE REDUCE-IT Launch Date Lebanon March 2018 August 2021 June 2018 United Arab Emirates July 2018 October 2021 February 2019 Qatar December 2019 April 2021 — Bahrain April 2021 April 2022 — Kuwait December 2021 — — Saudi Arabia March 2022 — — VASCEPA is under registration in additional countries in the MENA region.
Biologix obtained approval of VASCEPA under the MARINE and REDUCE-IT indications, and subsequently launched commercially in the following countries: Country MARINE REDUCE-IT Launch Date Lebanon March 2018 August 2021 June 2018 United Arab Emirates July 2018 October 2021 February 2019 Qatar December 2019 April 2021 N/A Bahrain April 2021 April 2022 N/A Kuwait December 2021 March 2023 September 2023 Saudi Arabia March 2022 June 2023 September 2023 VASCEPA is under registration in additional countries in the MENA region.
Other states or localities may have laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; restrict the ability of manufacturers to offer co-pay support to patients for certain prescription drugs; require drug manufacturers to report information related to clinical trials, or information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; relate to insurance fraud in the case of claims involving private insurers; and/or require identification or licensing of sales representatives.
Other states or localities may have laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; restrict the ability of manufacturers to offer co-pay support to patients for certain prescription drugs; require drug manufacturers to report information related to clinical trials, or information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; relate to insurance fraud in the case of claims involving private insurers; and/or require identification or licensing of sales representatives. 18 Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring manufacturers to report information related to payments to physicians and other healthcare providers, marketing expenditures, and drug pricing information.
Financial Information The financial information required under this Item 1 is incorporated herein by reference to Item 8 of this Annual Report on Form 10-K. 28
Financial Information The financial information required under this Item 1 is incorporated herein by reference to Item 8 of this Annual Report on Form 10-K. 25
United States Heart attacks, strokes and other cardiovascular events represent the leading cause of death and disability among men and women in western societies. According to the Heart Disease and Stroke Statistics—2022 Update from the AHA, CVD is the underlying cause of death in approximately one out of every three deaths – one death approximately every 36 seconds.
United States Heart attacks, strokes and other cardiovascular events represent the leading cause of death and disability among men and women in western societies. According to the Heart Disease and Stroke Statistics—2023 Update from the AHA, CVD is the underlying cause of death in approximately one out of every three deaths – one death approximately every 34 seconds.
Approximately 127 million adults in the United States live with one or more types of cardiovascular disease with an estimated 1 million new or recurrent coronary events and 795,000 new or recurrent strokes occurring each year.
Approximately 130 million adults in the United States live with one or more types of cardiovascular disease with an estimated one million new or recurrent coronary events and 795,000 new or recurrent strokes occurring each year.
It is estimated that more than 50 million adults in the United States have elevated triglyceride levels ≥150 mg/dL. Additionally, approximately 2 to 3 million adults in the United States have very high triglyceride levels ( 500 mg/dL), the condition for which VASCEPA received its initial drug approval from the U.S.
It is estimated that more than 50 million adults in the United States have elevated triglyceride levels ≥150 mg/dL. Additionally, approximately two to three million adults in the United States have very high triglyceride levels ( 500 mg/dL), the condition for which VASCEPA received its initial drug approval from the U.S.
On November 10, 2018, we announced primary results from our REDUCE-IT study as late-breaking clinical results at the 2018 Scientific Sessions of the AHA and the results were concurrently published in The New England Journal of Medicine .
On November 10, 2018, we announced primary results from our REDUCE-IT study as late-breaking clinical results at the 2018 Scientific Sessions of the American Heart Association, or AHA, and the results were concurrently published in The New England Journal of Medicine .
Since VASCEPA was made commercially available in 2013, more than twenty million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health. In 2020, following our unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr. Reddy’s Laboratories, Inc., or Dr.
Since VASCEPA was made commercially available in 2013, approximately 25 million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health. In 2020, following our unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr. Reddy’s Laboratories, Inc., or Dr.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, ensuring certain accountability measures are in place and taking certain measures when engaging third-party processors.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, legal basis for processing personal data which may include obtaining consent of the individuals to whom the personal data relates, providing detailed information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, ensuring certain accountability measures are in place and taking certain measures when engaging third-party processors.
There are many pharmaceutical companies, biotechnology companies, public and private universities and research organizations actively engaged in the research and development of products that may be similar to our product. It is probable that the number of companies seeking to develop products and therapies similar to our product will increase.
There are many pharmaceutical companies, biotechnology companies, public and private universities and research organizations actively engaged in the research and development of products that may be similar to our product. It is probable that the number of companies seeking to develop products and therapies similar to our product or within the same therapeutic category will increase.
FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in all or most foreign countries prior to the commencement of clinical trials or marketing of the product in those countries.
Whether or not we obtain U.S. FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in all or most foreign countries prior to the commencement of clinical trials or marketing of the product in those countries.
An estimated 28 million adults 20 years of age have high total serum cholesterol levels ( 240 mg/dL), and an estimated 70 million adults 20 years of age have borderline high or high low-density lipoprotein (“bad”) cholesterol, or LDL-C, levels ( 130 mg/dL).
An estimated 25 million adults 20 years of age have high total serum cholesterol levels ( 240 mg/dL), and an estimated 65 million adults 20 years of age have borderline high or high low-density lipoprotein (“bad”) cholesterol, or LDL-C, levels ( 130 mg/dL).
Available Information Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K (including exhibits), and amendments to reports filed pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, are made available free of charge on or through our website at www.amarincorp.com as soon as reasonably practicable after such reports are filed with, or furnished to, the Securities and Exchange Commission, or SEC.
Ester Neurosciences Limited had no operating activities. 24 Available Information Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K (including exhibits), and amendments to reports filed pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, are made available free of charge on or through our website at www.amarincorp.com as soon as reasonably practicable after such reports are filed with, or furnished to, the Securities and Exchange Commission, or SEC.
Through the date of this Annual Report on Form 10-K, we have received and made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.
Through the date of this Annual Report, we have received and made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.
Additionally, under the Food and Drug Omnibus Reform Act of 2022, or FDORA, sponsors of approved drugs must provide six months’ notice to the FDA of any changes in marketing status, such as the withdrawal of a drug, and failure to do so could result in the 13 FDA placing the product on a list of discontinued products, which would revoke the product’s ability to be marketed.These are viable risks once a product is on the market.
Additionally, under the Food and Drug Omnibus Reform Act of 2022, or FDORA, sponsors of approved drugs must provide six months’ notice to the FDA of any changes in marketing status, such as the withdrawal of a drug, and failure to do so could result in the FDA placing the product on a list of discontinued products, which would revoke the product’s ability to be marketed.
In 2022, we reviewed our contractual supplier purchase obligations and have taken steps to amend supplier agreements to align supply arrangements with current and future market demand, while we decrease our current inventory levels primarily related to North America approved inventory.
Beginning in 2022, we reviewed our contractual supplier purchase obligations and began taking steps to amend supplier agreements to align supply arrangements with current and future market demand, while we decrease our current inventory levels primarily related to North America approved inventory.
If our promotional activities or other operations are found to be in violation of any of the laws described above or any other governmental regulations or guidance that apply to us through existing or new interpretations, we may be subject to prolonged litigation, penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, the exclusion from participation in federal and state healthcare programs, individual imprisonment, reputational harm and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business. 19 If our promotional activities or other operations are found to be in violation of any of the laws described above or any other governmental regulations or guidance that apply to us through existing or new interpretations, we may be subject to prolonged litigation, penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, the exclusion from participation in federal and state healthcare programs, individual imprisonment, reputational harm and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
The Medicaid Drug Rebate program, 340B program, and VA/FSS pricing program, and the risks relating to price reporting and other obligations under these programs, are further discussed under the heading “ If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects ” in Part I, Item 1A of this Annual Report on Form 10-K.
The Medicaid Drug Rebate program, 340B program, and VA/FSS pricing program, and the risks relating to price reporting and other obligations under these programs, are further discussed under the heading “ If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects ” in Part I, Item 1A of this Annual Report on Form 10-K. 21 Outside the United States, ensuring coverage and adequate payment for a product also involves challenges.
FDA approved indication and label expansion in December 2019) The REDUCE-IT study was designed to evaluate the efficacy of VASCEPA in reducing major cardiovascular events in an at-risk patient population also receiving statin therapy.
FDA approved indication and label expansion in December 2019; basis for EU EC approved indication and label in March 2021)) The REDUCE-IT study was designed to evaluate the efficacy of VASCEPA in reducing major cardiovascular events in an at-risk patient population also receiving statin therapy.
As of December 31, 2022, we had inventory of $392.4 million, of which approximately 90% is inventory approved for use in North America. We continue to negotiate with our contract suppliers to align our supply arrangements with current and future global market demand. Competition General The biotechnology and pharmaceutical industries are highly competitive.
As of December 31, 2023, we had inventory of $336.2 million, of which approximately 80% is inventory approved for use in North America. We continue to negotiate with our contract suppliers to align our supply arrangements with current and future global market demand. Competition General The biotechnology and pharmaceutical industries are highly competitive.
In China and the Middle East, we are pursuing such regulatory approvals and subsequent commercialization of VASCEPA with commercial partners. The EC approval provides ten years of market protection in the EU.
We are pursuing additional regulatory approvals for VASCEPA in Europe, China and the Middle East. In China and the Middle East, we are pursuing such regulatory approvals and subsequent commercialization of VASCEPA with commercial partners. The EC approval provides 10 years of market protection in the EU.
FDA approval with labeling consistent with the MARINE indication and have entered the U.S. market with a 1-gram capsule: Company FDA MARINE Indication Approval Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 Teva Pharmaceuticals USA, Inc. September 2020 September 2022 (1) Apotex, Inc.
FDA approval with labeling consistent with the MARINE indication and have entered the U.S. market: Company FDA MARINE Indication Approval 1-gram Launch Date 0.5-gram Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 March 2023 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 June 2023 Teva Pharmaceuticals USA, Inc. September 2020 January 2023 September 2022 Apotex, Inc.
For example, in order to transfer data outside of the EEA or the UK to a non-adequate country, the GDPR and UK GDPR (as applicable) requires us to enter into an appropriate transfer mechanism, and may require us to take additional steps to ensure an essentially equivalent level of data protection.
For example, in order to transfer data outside of the EEA or the UK to a non-adequate country, the GDPR requires us to enter into an appropriate transfer mechanism, and may require us to take additional steps to ensure an essentially equivalent level of data protection, including carrying out transfer impact assessments.
In certain countries, such as Denmark, individual patient reimbursement is allowed prior to national, general organization reimbursement. In countries where individual price reimbursement allowed prior to national reimbursement, product can be made available on a patient by patient basis, while national reimbursement negotiations are ongoing. In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic.
In countries where individual price reimbursement is allowed prior to national reimbursement, product can be made available on a patient-by-patient basis, while the national reimbursement negotiations are ongoing. In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic.
Organizational Structure At March 1, 2023, we had the following subsidiaries: Subsidiary Name Country of Incorporation or Registration Proportion of Ownership Interest and Voting Power Held Amarin Pharmaceuticals Ireland Limited Ireland 100% Amarin Pharma, Inc.
Organizational Structure At February 29, 2024, we had the following subsidiaries: Subsidiary Name Country of Incorporation or Registration Proportion of Ownership Interest and Voting Power Held Amarin Pharmaceuticals Ireland Limited Ireland 100% Amarin Pharma, Inc.
On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. 22 In August 2022, the Inflation Reduction Act of 2022, or IRA was signed into law.
On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
We have completed the first of a three year plan to submit and obtain regulatory approval in 20 additional countries in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.
Other We completed the second year of a three-year plan to submit and obtain regulatory approval in 20 or more additional countries and regions in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.
FDA approval with labeling consistent with the MARINE indication of VASCEPA, have entered the U.S. market and represent our main competitors: 10 Company FDA MARINE Indication Approval Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 Teva Pharmaceuticals USA, Inc. September 2020 September 2022 (1) Apotex, Inc.
FDA approval with labeling consistent with the MARINE indication of VASCEPA, have entered the U.S. market and represent our main competitors: Company FDA MARINE Indication Approval 1-gram Launch Date 0.5-gram Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 March 2023 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 June 2023 Teva Pharmaceuticals USA, Inc.
The active arm of the study was comprised of patients on optimized statin therapy plus VASCEPA. All subjects enrolled in the study had elevated triglyceride levels and either established coronary heart disease or risk factors for coronary heart disease. In August 2011, we reached agreement with the U.S.
The active arm of the study was comprised of patients on optimized statin therapy plus VASCEPA. All subjects enrolled in the study had elevated triglyceride levels and either established coronary heart disease or risk factors for coronary heart disease.
According to the Cardiovascular Disease: A Costly Burden for America Projections Through 2035 from the AHA, 45% of the United States population is projected to have some form of CVD by 2035 and total costs of CVD are expected to reach $1.1 trillion in 2035, with direct medical costs projected to reach $749.0 billion and indirect costs estimated to reach $368.0 billion.
According to the Cardiovascular Disease: A Costly Burden for America Projections Through 2035 from the AHA, 45% of the United States population is projected to have some form of CVD by 2035 and total costs of CVD are expected to reach $1.1 trillion in 2035.
An additional seven secondary endpoints were achieved below the key secondary endpoint, in order of sequential statistical testing within the prespecified hierarchy: • Cardiovascular death or nonfatal heart attack: 25% RRR (p • Fatal or nonfatal heart attack: 31% RRR (p • Urgent or emergent revascularization: 35% RRR (p 5 • Cardiovascular death: 20% RRR (p=0.03) • Hospitalization for unstable angina: 32% RRR (p=0.002) • Fatal or nonfatal stroke: 28% RRR (p=0.01) • Total mortality, nonfatal heart attack or nonfatal stroke: 23% RRR (p The next prespecified secondary endpoint in the hierarchy was the only such endpoint that did not achieve statistical significance although it trended positively: • Total mortality, which includes mortality from non-cardiovascular and cardiovascular events: 13% RRR (p=0.09) Positive REDUCE-IT results were consistent across various patient subgroups, including female/male, diabetic/non-diabetic and secondary/primary prevention.
NNT is a statistical concept intended to provide a measurement of the impact of a medicine or therapy by estimating the number of patients that need to be treated in order to have an impact on one person. 5 An additional seven secondary endpoints were achieved below the key secondary endpoint, in order of sequential statistical testing within the prespecified hierarchy: • Cardiovascular death or nonfatal heart attack: 25% RRR (p • Fatal or nonfatal heart attack: 31% RRR (p • Urgent or emergent revascularization: 35% RRR (p • Cardiovascular death: 20% RRR (p=0.03) • Hospitalization for unstable angina: 32% RRR (p=0.002) • Fatal or nonfatal stroke: 28% RRR (p=0.01) • Total mortality, nonfatal heart attack or nonfatal stroke: 23% RRR (p The next prespecified secondary endpoint in the hierarchy was the only such endpoint that did not achieve statistical significance although it trended positively: • Total mortality, which includes mortality from non-cardiovascular and cardiovascular events: 13% RRR (p=0.09) Positive REDUCE-IT results were consistent across various patient subgroups, including female/male, diabetic/non-diabetic and secondary/primary prevention.
Coverage and reimbursement for drug products can differ significantly from payor to payor. The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved.
The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved.
The federal civil and criminal false claim laws, including the civil monetary penalty laws and the civil False Claims Act prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of government funds, or knowingly making or using, or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly concealing, or knowingly and improperly avoiding, decreasing, or concealing an obligation to pay money or transmit properly to the federal government.
We continue to evaluate what effect, if any, these rules will have on our business. 17 The federal civil and criminal false claim laws, including the civil monetary penalty laws and the civil False Claims Act prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of government funds, or knowingly making or using, or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly concealing, or knowingly and improperly avoiding, decreasing, or concealing an obligation to pay money or transmit properly to the federal government.
In all cases, the clinical trials must be conducted in accordance with GCP, which have their origin in the World Medical Association’s Declaration of Helsinki, the applicable regulatory requirements, and guidelines developed by the International Conference on Harmonization, or ICH, for GCP practices in clinical trials. 16 Fraud and Abuse Laws and Data Regulation In addition to U.S.
In all cases, the clinical trials must be conducted in accordance with GCP, which have their origin in the World Medical Association’s Declaration of Helsinki, the applicable regulatory requirements, and guidelines developed by the International Conference on Harmonization, or ICH, for GCP practices in clinical trials.
In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final National Medical Products Administration, or NMPA, review of the VASCEPA NDA was initiated with Edding expecting approval by the end of 2022.
In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final NMPA review of the VASCEPA NDA was initiated.
FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws restrict certain marketing practices in the biopharmaceutical industry. These laws include Anti-Kickback Statutes and false claims statutes.
Fraud and Abuse Laws and Data Regulation In addition to U.S. FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws restrict certain marketing practices in the biopharmaceutical industry. These laws include Anti-Kickback Statutes and false claims statutes.
Operating activity being conducted by the European subsidiaries were in support of Amarin Pharmaceuticals Ireland Limited. Ester Neurosciences Limited had no operating activities.
Operating activity being conducted by the European subsidiaries were in support of Amarin Pharmaceuticals Ireland Limited.
On January 24, 2023, the MHRA announced that a new international recognition framework will be put in place from January 1, 2024. Under this new framework, the MHRA will have regard to decisions on the approval of a marketing authorization made by the EMA and certain other regulators when considering whether to grant a UK marketing authorization.
On January 1, 2024, a new international recognition framework was put in place by the MHRA under which the MHRA may have regard to decisions on the approval of a marketing authorization made by the EMA and certain other regulators when considering whether to grant a UK marketing authorization.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThe following is a brief summary of some of the most important rules of the Takeover Code which, as noted, does not apply to us: • In connection with a potential offer, if following an approach by or on behalf of a potential bidder, the company is “the subject of rumor or speculation” or there is an “untoward movement” in the company’s share price, there is a requirement for the potential bidder to make a public announcement about a potential offer for the company, or for the company to make a public announcement about the potential offer. • When a person or group of persons who are treated as “acting in concert” with each other (a) acquires interests in shares carrying 30% or more of the voting rights of a company (which percentage is treated by the Takeover Code as the level at which effective control is obtained) or (b) increases the aggregate percentage interest they have when they are already interested in not less than 30% and not more than 50%, they must make a cash offer to all other shareholders at the highest price paid by them in the 12 months before the offer was announced. • When interests in shares of any class representing 10% of shares of that class have been acquired for cash by an offeror (i.e., a bidder) during the offer period (i.e., broadly speaking, the period after the potential offer has been made public) and within 12 months prior to commencement of the offer period, the offer must be in cash or be accompanied by a cash alternative for all shareholders of that class at the highest price paid by the offeror in that period.
Biggest changeThe following is a brief summary of some of the most important rules of the Takeover Code which, as noted, does not apply to us: • In connection with a potential offer, if following an approach by or on behalf of a potential bidder, the company is “the subject of rumor or speculation” or there is an “untoward movement” in the company’s share price, there is a requirement for the potential bidder to make a public announcement about a potential offer for the company, or for the company to make a public announcement about the potential offer. • When any person acquires, whether by a series of transactions over a period of time or not, an interest in shares which (taken together with shares already held by that person and an interest in shares held or acquired by persons acting in concert with him or her) carry 30% or more of the voting rights of a company that is subject to the Takeover Code, that person is generally required to make a mandatory offer to all the holders of any class of equity share capital or other class of transferable securities carrying voting rights in that company to acquire the balance of their interests in the company. 55 • When any person who, together with persons acting in concert with him or her, is interested in shares representing not less than 30% but does not hold more than 50% of the voting rights of a company that is subject to the Takeover Code, and such person, or any person acting in concert with him or her, acquires an additional interest in shares which increases the percentage of shares carrying voting rights in which he or she is interested, then such person is generally required to make a mandatory offer to all the holders of any class of equity share capital or other class of transferable securities carrying voting rights of that company to acquire the balance of their interests in the company. • A mandatory offer triggered in the circumstances described in the two paragraphs above must be in cash (or be accompanied by a cash alternative) and at not less than the highest price paid within the preceding 12 months to acquire any interest in shares in the company by the person required to make the offer or any person acting in concert with him or her. • In relation to a voluntary offer (i.e., any offer which is not a mandatory offer), when interests in shares of any class representing 10% of shares of that class have been acquired for cash by an offeror (i.e., a bidder) and any person acting in concert with it during the offer period (i.e., broadly speaking, the period after the potential offer has been made public) and within 12 months prior to commencement of the offer period, the offer must be in cash or be accompanied by a cash alternative for all shareholders of that class at not less than the highest price paid for any interest in shares of that class by the offeror in that period.
International reference pricing, or IRP, has been widely used by many countries outside of the United States to control costs based on an external benchmark of a product’s price in other countries. IRP policies can change quickly and frequently and may not reflect differences in the burden of disease, indications, market structures, or affordability differences across countries or regions.
International reference pricing, or IRP, has been widely used by many countries outside the United States to control costs based on an external benchmark of a product’s price in other countries. IRP policies can change quickly and frequently and may not reflect differences in the burden of disease, indications, market structures, or affordability differences across countries or regions.
This dynamic and resulting regulatory scrutiny could be costly for us and could negatively and materially interfere with our business plans. The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, often requires considerable advanced planning and necessitates long-term financial commitments to ensure sufficient capacity is available when needed.
This dynamic and resulting regulatory scrutiny could be costly for us and could negatively and materially interfere with our business plans. The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, and often requires considerable advanced planning and necessitates long-term financial commitments to ensure sufficient capacity is available when needed.
VASCEPA is a prescription-only omega-3 fatty acid product. Omega-3 fatty acids are also marketed by other companies as non-prescription dietary supplements. As a result, in the U.S., VASCEPA is subject to non-prescription competition and consumer substitution. Our only product, VASCEPA, is a prescription-only form of EPA, an omega-3 fatty acid in ethyl ester form.
Omega-3 fatty acids are also marketed by other companies as non-prescription dietary supplements. As a result, in the U.S., VASCEPA is subject to non-prescription competition and consumer substitution. Our only product, VASCEPA, is a prescription-only form of EPA, an omega-3 fatty acid in ethyl ester form.
FDA or the EC: • the magnitude of the treatment benefit and related risks on the primary composite endpoint, its components, secondary endpoints and the primary and secondary risk prevention cohorts; • consideration of which components of the composite or secondary endpoints have the most clinical significance; • the consistency of the primary and secondary outcomes; • the consistency of findings across cohorts and important subgroups; • safety considerations and risk/benefit considerations (such as those related to adverse events, including bleeding and atrial fibrillation generally and in different sub-populations); • consideration of REDUCE-IT results in the context of other clinical studies; • consideration of the cumulative effect of VASCEPA in studied patients; and • study conduct and data quality, integrity and consistency, including aspects such as analyses regarding the placebo used in REDUCE-IT and other studies of VASCEPA and its impact, if any, on the reliability of clinical data.
FDA or the EC: • the magnitude of the treatment benefit and related risks on the primary composite endpoint, its components, secondary endpoints and the primary and secondary risk prevention cohorts; • consideration of which components of the composite or secondary endpoints have the most clinical significance; 31 • the consistency of the primary and secondary outcomes; • the consistency of findings across cohorts and important subgroups; • safety considerations and risk/benefit considerations (such as those related to adverse events, including bleeding and atrial fibrillation generally and in different sub-populations); • consideration of REDUCE-IT results in the context of other clinical studies; • consideration of the cumulative effect of VASCEPA in studied patients; and • study conduct and data quality, integrity and consistency, including aspects such as analyses regarding the placebo used in REDUCE-IT and other studies of VASCEPA and its impact, if any, on the reliability of clinical data.
Depending on the circumstances, failure to meet applicable regulatory requirements can result in significant civil, criminal and administrative penalties, damages, fines, disgorgement, individual imprisonment, exclusion from participation in federal and state funded healthcare programs (such as Medicare and Medicaid), contractual damages and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
Depending on the circumstances, failure to meet applicable regulatory requirements can result in significant civil, criminal and administrative penalties, damages, fines, disgorgement, individual imprisonment, exclusion from participation in federal and state 46 funded healthcare programs (such as Medicare and Medicaid), contractual damages and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
You should be aware, however, that the voting rights of ADSs are also governed by the provisions of a deposit agreement with our depositary bank. • Under English law, subject to certain exceptions and disapplications, each shareholder generally has preemptive rights to subscribe on a proportionate basis to any issuance of ordinary shares or rights to subscribe for, or to convert securities into, ordinary shares for cash.
You should be aware, however, that the voting rights of ADSs are also governed by the provisions of a deposit agreement with our depositary bank. 54 • Under English law, subject to certain exceptions and disapplications, each shareholder generally has preemptive rights to subscribe on a proportionate basis to any issuance of ordinary shares or rights to subscribe for, or to convert securities into, ordinary shares for cash.
Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects. Changes in reimbursement procedures by government and other third-party payors may limit our ability to market and sell our approved drugs.
Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects. 38 Changes in reimbursement procedures by government and other third-party payors may limit our ability to market and sell our approved drugs.
Some third-party payor benefit packages restrict reimbursement, charge copayments to patients, or do not provide coverage for specific drugs or drug classes. In addition, certain U.S. based healthcare providers are moving toward a managed care system in which such providers contract to provide comprehensive healthcare services, including prescription drugs, for a fixed cost per person.
Some third-party payor benefit packages restrict reimbursement, charge copayments to patients, or do not provide coverage for specific drugs, uses, or drug classes. In addition, certain U.S.-based healthcare providers are moving toward a managed care system in which such providers contract to provide comprehensive healthcare services, including prescription drugs, for a fixed cost per person.
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the 51 improper use of information obtained in the course of patient recruitment for clinical trials. Refer to “ Item 1.
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the improper use of information obtained in the course of patient recruitment for clinical trials. Refer to “ Item 1.
FDA, including communications in connection with its review of the ANCHOR indication for VASCEPA, it is our understanding that the U.S. FDA is not prepared to approve any therapy for treatment of cardiovascular risk based on biomarker modification without cardiovascular outcomes study data, with the potential exception of therapies which lower LDL-cholesterol, depending on the circumstances.
FDA, including communications in connection with its review of the ANCHOR indication for VASCEPA, it is our understanding that the U.S. FDA is not prepared to approve any therapy for treatment of CV risk based on biomarker modification without cardiovascular outcomes study data, with the potential exception of therapies which lower LDL-cholesterol, depending on the circumstances.
The failure to recruit key scientific, technical and management personnel would be detrimental to our ability to implement our business plan. 54 Our internal computer systems, or those of our third‑party clinical research organizations or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our commercial, research and development and other programs.
The failure to recruit key scientific, technical and management personnel would be detrimental to our ability to implement our business plan. Our internal computer systems, or those of our third‑party clinical research organizations or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our commercial, research and development and other programs.
Although the outcome of tax audits is always uncertain and could result in significant cash tax payments, we do not believe the outcome of any ongoing or future audits will have a material adverse effect on our consolidated financial position or results of operations. We could be adversely affected by our exposure to customer concentration risk.
Although the outcome of tax audits is always uncertain and could result in significant cash tax payments, we do not believe the outcome of any ongoing or future audits will have a material adverse effect on our consolidated financial position or results of operations. 50 We could be adversely affected by our exposure to customer concentration risk.
We rely on trade secrets to protect technology in cases when we believe patent protection is not appropriate or obtainable. However, trade secrets are difficult to protect. While we require certain of our academic collaborators, contractors and consultants to enter into confidentiality agreements, we may not be able to adequately protect our trade secrets or other proprietary information.
We rely on trade secrets to protect technology in cases when we believe patent protection is not appropriate or obtainable. However, trade secrets are difficult to protect. While we require certain of our academic collaborators, contractors and 48 consultants to enter into confidentiality agreements, we may not be able to adequately protect our trade secrets or other proprietary information.
Any allegations that our promotional activities are not truthful or misleading, even allegations without merit, could cause reputational harm and adversely affect our ability to operate our business and our results of operations. 36 We may not be able to compete effectively against our competitors’ pharmaceutical product, including generic products.
Any allegations that our promotional activities are not truthful or misleading, even allegations without merit, could cause reputational harm and adversely affect our ability to operate our business and our results of operations. We may not be able to compete effectively against our competitors’ pharmaceutical product, including generic products.
The resources of our suppliers vary and are limited; costs associated with projected expansion and qualification can be significant, and lead-times for supply purchases and capacity expansion are long requiring certain supply related decisions and commitment to be made in advance of 48 commercial launch, including in China and various European countries.
The resources of our suppliers vary and are limited; costs associated with projected expansion and qualification can be significant, and lead-times for supply purchases and capacity expansion are long requiring certain supply related decisions and commitment to be made in advance of commercial launch, including in China and various European countries.
In many markets around the world, these payors, including 32 government health systems, private health insurers and other organizations, remain focused on reducing the cost of healthcare, and their efforts have intensified as a result of rising healthcare costs and economic challenges. Drugs remain heavily scrutinized for cost containment.
In many markets around the world, these payors, including government health systems, private health insurers and other organizations, remain focused on reducing the cost of healthcare, and their efforts have intensified as a result of rising healthcare costs and economic challenges. Drugs remain heavily scrutinized for cost containment.
The degree of market acceptance of VASCEPA for its approved indications and uses or otherwise will depend on a number of factors, including: • the impact of and outcome of adjudicated, settled and pending patent litigation; • the commercialization and pricing of any current or potential generic versions of VASCEPA; • the perceived efficacy and safety of VASCEPA by prescribing healthcare professionals and patients, as compared to no treatment and as compared to alternative treatments in various at-risk patient populations; • the prevalence and severity of any side effects and warnings in VASCEPA's approved labeling internationally; • peer review of different elements of data supporting our REDUCE-IT indication over time; • continued review and analysis of the results of our clinical data supporting our REDUCE-IT indication by regulatory authorities internationally; • our ability to offer VASCEPA for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the scope, effectiveness and strength of product education, marketing and distribution support, including our sales and marketing teams; • publicity concerning VASCEPA or competing products; • our ability to continually promote VASCEPA in the United States consistent with and outside of U.S.
The degree of market acceptance of VASCEPA for its approved indications and uses or otherwise will depend on a number of factors, including: 30 • the impact of and outcome of adjudicated, settled and pending patent litigation; • the commercialization and pricing of any current or potential generic versions of VASCEPA; • the perceived efficacy and safety of VASCEPA by prescribing healthcare professionals and patients, as compared to no treatment and as compared to alternative treatments in various at-risk patient populations; • the prevalence and severity of any side effects and warnings in VASCEPA's approved labeling internationally; • peer review of different elements of data supporting our REDUCE-IT indication over time; • continued review and analysis of the results of our clinical data supporting our REDUCE-IT indication by regulatory authorities internationally; • our ability to offer VASCEPA for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try our therapies and of physicians to prescribe these therapies; • the scope, effectiveness and strength of product education, marketing and distribution support, including our sales and marketing teams; • publicity concerning VASCEPA or competing products; • our ability to continually promote VASCEPA in the United States consistent with U.S.
Such proceedings may review the patentability of one or more claims in a patent on specified substantive grounds such as allegations that a claim is obvious on the basis of certain prior art. We cannot predict the outcome of the pending lawsuits, any appeals, or any subsequently filed lawsuits or inter partes review.
Such proceedings may review the patentability of one or more claims in a patent on specified substantive grounds such as allegations that a claim is obvious on the basis of certain prior art. 34 We cannot predict the outcome of the pending lawsuits, any appeals, or any subsequently filed lawsuits or inter partes review.
For example, proposals are being considered to expand the use of dietary supplements in addition to or in place of drugs in government and private payor plans. In addition, cost control initiatives could decrease the price that we or any potential collaborators could receive for any of our future products and could adversely affect our profitability.
Proposals are being considered to expand the use of dietary supplements in addition to or in place of drugs in government and private payor plans. In addition, cost control initiatives could decrease the price that we or any potential collaborators could receive for any of our future products and could adversely affect our profitability.
For example, the Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and EPA (RESPECT-EPA; UMIN Clinical Trials Registry number, UMIN000012069) is a study examining Japanese patients with chronic coronary artery disease receiving LDL-C lowering treatment by statin therapy.
The Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and EPA (RESPECT-EPA; UMIN Clinical Trials Registry number, UMIN000012069) is a study examining Japanese patients with chronic coronary artery disease receiving LDL-C lowering treatment by statin therapy.
In addition, we could be subject to regulatory actions and/or claims made by individuals and groups in private litigation involving privacy issues related to data collection and use practices and other data privacy laws and regulations, including claims for misuse or inappropriate disclosure of data, as well as unfair or deceptive practices.
In addition, we could be subject to regulatory actions and/or claims made by individuals and groups in 49 private litigation involving privacy issues related to data collection and use practices and other data privacy laws and regulations, including claims for misuse or inappropriate disclosure of data, as well as unfair or deceptive practices.
Although, we intend to vigorously defend our intellectual property rights related to VASCEPA, there can be no assurance that we will be successful in preventing use of generic versions of VASCEPA in indications for which they have not been approved by U.S.
Although, we intend to vigorously defend our intellectual property rights related to VASCEPA, there can be no assurance that we will be successful in preventing use of generic versions of VASCEPA in indications for which they have not been approved by the U.S.
If we are unable to 56 consistently generate robust product revenues, we will not become profitable on a sustained basis in the near term, if ever, and may be unable to continue operations without continued funding. Our operating results are unpredictable and may fluctuate.
If we are unable to consistently generate robust product revenues, we will not become profitable on a sustained basis in the near term, if ever, and may be unable to continue operations without continued funding. Our operating results are unpredictable and may fluctuate.
In addition, in the case of the third-party manufacturers that supply any future product candidates, changes in manufacturers often involve changes in manufacturing procedures and processes, which could require that we conduct bridging studies between our prior clinical supply used in our clinical trials and that of any new manufacturer.
In addition, in the case of the third-party manufacturers that supply our product candidates, changes in manufacturers often involve changes in manufacturing procedures and processes, which could require that we conduct bridging studies between our prior clinical supply used in our clinical trials and that of any new manufacturer.
There are many pharmaceutical companies, biotechnology companies, public and private universities and research organizations actively engaged in the research and development of products that may be similar to our product. We expect that the number of companies seeking to develop products and therapies similar to VASCEPA will increase.
There are many pharmaceutical companies, biotechnology companies, public and private universities and research organizations actively engaged in the research and development of products that may be similar to our product. We expect that the number of companies seeking to develop products and therapies similar to VASCEPA may increase.
The failure of clinical trials to demonstrate safety and efficacy for our desired indications could harm the development of that product candidate as well as other product candidates, and our business and results of operations would suffer. For example, in connection with U.S.
The failure of clinical trials to demonstrate safety and efficacy for our desired indications could harm the development of that product candidate as well as other product candidates, and our business and results of operations would suffer. In connection with U.S.
Federal law requires that any company that participates in the Medicaid Drug Rebate program also participate in the Public Health Service’s 340B drug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.
Federal law requires that any company that participates in the Medicaid Drug Rebate program also participate in the Public Health Service’s 340B drug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid 37 and Medicare Part B.
Our aggregate capacity to produce API is dependent upon the continued qualification of our API suppliers and, depending on the ability of existing suppliers to meet our supply demands, and the ability to qualify any new suppliers. If no additional API supplier is approved by the U.S.
Our aggregate capacity to produce API is dependent upon the continued qualification of our API suppliers 43 and, depending on the ability of existing suppliers to meet our supply demands, the ability to qualify any new suppliers. If no additional API supplier is approved by the U.S.
We are currently, and may continue to be, substantially dependent on third parties for our international efforts, and we may not be 50 successful in negotiating or establishing relationships with business partners to support and maintain control over our international activities.
We are currently, and may continue to be, substantially dependent on third parties for our international efforts, and we may not be successful in negotiating or establishing relationships with business partners to support and maintain control over our international activities.
Negative economic conditions would likely have a negative effect on our ability to obtain financing on acceptable terms. 62 While we may seek additional funding through public or private financings, we may not be able to obtain financing on acceptable terms, or at all.
Negative economic conditions would likely have a negative effect on our ability to obtain financing on acceptable terms. While we may seek additional funding through public or private financings, we may not be able to obtain financing on acceptable terms, or at all.
In addition, if we are required to change third-party manufacturer for any reason, we will be required to verify that the new third-party manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations.
In addition, if we are required to change a third-party manufacturer for any reason, we will be required to verify that the new third-party manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations.
For example, Edding is responsible for development and commercialization activities in the China Territory and associated expenses under our development, commercialization and supply agreement with them. Additionally, Edding is required to conduct clinical trials in the China Territory to secure regulatory approval in certain territories.
Edding is responsible for development and commercialization activities in the China Territory and associated expenses under our development, commercialization and supply agreement with them. Additionally, Edding is required to conduct clinical trials in the China Territory to secure regulatory approval in certain territories.
The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture, often requires considerable advanced planning and long-term financial commitments to ensure sufficient capacity is available when needed.
The active pharmaceutical ingredient in VASCEPA is difficult and time consuming to manufacture. It often requires considerable advanced planning and long-term financial commitments to ensure sufficient capacity is available when needed.
Such restatements and recalculations increase our costs for 42 complying with the laws and regulations governing the Medicaid Drug Rebate program and could result in an overage or underage in our rebate liability for past quarters.
Such restatements and recalculations increase our costs for complying with the laws and regulations governing the Medicaid Drug Rebate program and could result in an overage or underage in our rebate liability for past quarters.
FDA were to change this position, it could potentially have a negative impact on us by making it easier for other products to achieve a cardiovascular risk reduction indication without the need in advance to conduct a long and expensive cardiovascular outcomes study. VASCEPA also faces competition from dietary supplement manufacturers marketing omega-3 products as nutritional supplements.
FDA were to change this position, it could potentially have a negative impact on us by making it easier for other products to achieve a CV risk reduction indication without the need in advance to conduct a long and expensive CV outcomes study. VASCEPA also faces competition from dietary supplement manufacturers marketing omega-3 products as nutritional supplements.
For example, in Europe we have built out our team subsequent to EC approval of the marketing authorization acceptance in 2021, with plans to continue to expand our European staff as deemed appropriate on a country by country basis. The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.
In Europe we have built out our team subsequent to EC approval of the marketing authorization acceptance in 2021, with plans to continue to expand our European staff as deemed appropriate on a country-by-country basis. The time required to secure reimbursement tends to vary from country to country and cannot be reliably predicted at this time.
We may have difficulty identifying, attracting and integrating new executives to replace any such losses. As we expand commercialization efforts in Europe, we need to rapidly hire employees and ensure that they are well trained and working cohesively with core values which are consistent with our existing operations and which, we believe, help improve our position for success.
We may have difficulty identifying, attracting and integrating new executives to replace any such losses. As we pursue commercialization efforts in Europe, we need to rapidly hire employees and ensure that they are well trained and working cohesively with core values which are consistent with our existing operations and which, we believe, help improve our position for success.
Our future capital requirements will depend on many factors, including: • the timing, amount and consistency of revenue generated from the commercial sale of VASCEPA; 57 • the costs associated with commercializing VASCEPA in the United States and sales force sizing, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration; • continued costs associated with litigation and other legal proceedings and governmental inquiries; • the time and costs involved in obtaining additional regulatory approvals for VASCEPA based on REDUCE-IT results internationally; • the extent to which we continue to develop internally, acquire or in-license new products, technologies or businesses; and • the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights.
Our future capital requirements will depend on many factors, including: • the timing, amount and consistency of revenue generated from the commercial sale of VASCEPA; • the costs associated with commercializing VASCEPA in the United States, and for commercializing VAZKEPA in Europe, including hiring experienced professionals, and for additional regulatory approvals internationally, if any, the cost and timing of securing commercial supply of VASCEPA and the timing of entering into any new strategic collaboration with others relating to the commercialization of VASCEPA, if at all, and the terms of any such collaboration; • continued costs associated with litigation and other legal proceedings and governmental inquiries; • the time and costs involved in obtaining additional regulatory approvals for VASCEPA based on REDUCE-IT results internationally; • the extent to which we continue to develop internally, acquire or in-license new products, technologies or businesses; and • the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights.
As a result, payors are becoming more restrictive regarding the use of biopharmaceutical products and scrutinizing the prices of these products while requiring a higher level of clinical evidence to support the benefits such products bring to patients and the broader healthcare system. These pressures are intensified where our products are subject to competition, including from biosimilars.
As a result, payors are becoming more restrictive regarding the use of biopharmaceutical products and scrutinizing the prices of these products while requiring a higher level of clinical evidence to support the benefits such products bring to patients and the broader healthcare system. These pressures are intensified where our products are subject to competition, including from generics.
Collectively, these dynamics negatively affect our profitability for the sale of VASCEPA and could increase over time further impacting our operating results. Consolidation among these industry participants could increase the pressure on us from these market dynamics. The manufacture, packaging and distribution of pharmaceutical products such as VASCEPA are subject to U.S.
Collectively, these dynamics adversely affect our profitability for the sale of VASCEPA and could increase over time further impacting our operating results. Consolidation among these industry participants could increase the pressure on us from these market dynamics. The manufacture, packaging and distribution of pharmaceutical products such as VASCEPA are subject to U.S.
We are unable to predict the reimbursement policies employed by third-party healthcare payors may not be favorable to us.
We are unable to predict the reimbursement policies employed by third-party healthcare payors which may not be favorable to us.
We have been advised by our English solicitors that there is doubt as to the enforceability in England in original actions, or in actions for 61 enforcement of judgments of U.S. courts, of civil liabilities to the extent predicated upon the federal securities laws of the United States.
We have been 56 advised by our English solicitors that there is doubt as to the enforceability in England in original actions, or in actions for enforcement of judgments of U.S. courts, of civil liabilities to the extent predicated upon the federal securities laws of the United States.
Our financial condition and the success of our company will be materially adversely affected, we may have to further restructure our current operations, and our business prospects will be limited if we experience any negative developments relating to VASCEPA. For example, in the first quarter of 2020, the U.S.
Our financial condition and the success of our company will be materially adversely affected, we may have to further restructure our current operations, and our business prospects will be limited, if we experience any negative developments relating to VASCEPA. In the first quarter of 2020, the U.S.
Reddy’s, payors, and consumers, treble damages and other costs and fees. Injunctive relief against the alleged violative activities is also being sought by Dr. Reddy’s. Consumer group lawsuits followed claiming similar violations and alleging, for example, that such alleged violations resulted in higher prices to consumers.
Reddy’s, payors, and consumers, treble damages and other costs and fees. Injunctive relief against the alleged violative activities is also being sought by Dr. Reddy’s. Consumer group lawsuits followed claiming similar violations and alleging that such alleged violations resulted in higher prices to consumers.
Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of having federal funds being made available to the states for our drugs under Medicaid and Medicare Part B.
Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of having federal funds being made available to the states for our drugs under Medicaid and Medicare Part D.
For example, certain of our agreements with our suppliers include minimum purchase obligations and limited exclusivity provisions. These purchases are generally made on the basis of rolling 12-month forecasts which in part are binding on us and the balance of which are subject to adjustment by us subject to certain limitations.
Certain of our agreements with our suppliers include minimum purchase obligations and limited exclusivity provisions. These purchases are generally made on the basis of rolling 12-month forecasts which in part are binding on us and the balance of which are subject to adjustment by us subject to certain limitations.
There is a risk that there may not be sufficient liquidity 58 in the market to accommodate significant increases in selling activity or the sale of a large block of our securities. Our ADSs have historically had limited trading volume, which may also result in volatility.
There is a risk that there may not be sufficient liquidity in the market to accommodate significant increases in selling activity or the sale of a large block of our securities. Our ADSs have 53 historically had limited trading volume, which may also result in volatility.
We as an organization have limited experience in navigating the pricing and reimbursement regimes, outside of the United States, which foreign regimes are varied and complex, which might hinder our effectiveness in establishing satisfactory pricing, coverage and reimbursement levels in a timely manner or at all.
We as an organization have limited experience in navigating the pricing and reimbursement regimes outside of the United States. The foreign regimes are varied and complex, and this might hinder our effectiveness in establishing satisfactory pricing, coverage and reimbursement levels in a timely manner or at all.
FDA-approved use of our drug, to reduce severely high triglyceride levels, or the MARINE indication. We were unsuccessful in our appeals and our stock price was adversely and materially impacted by the ruling, the results of the appeals process and the introduction of generic competition.
FDA-approved use of our drug, to reduce severely high triglyceride levels, or the MARINE indication, or the ANDA litigation. We were unsuccessful in our appeals and our stock price was adversely and materially impacted by the ruling, the results of the appeals process and the introduction of generic competition.
In order to be eligible to have our products paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by certain federal agencies and grantees, as noted above, we participate in the VA’s FSS pricing program.
In order to be eligible to have our products paid for with federal funds under the Medicaid and Medicare Part D programs and purchased by certain federal agencies and grantees, as noted above, we participate in the VA’s FSS pricing program.
Our and our subsidiaries’ income tax returns are periodically examined by various tax authorities, including the Internal Revenue Service, or the IRS, and states. For example, the IRS began an examination of our 2018 U.S. income tax return in the first quarter of 2020.
Our and our subsidiaries’ income tax returns are periodically examined by various tax authorities, including the Internal Revenue Service, or the IRS, and state tax authorities. For example, the IRS began an examination of our 2018 U.S. income tax return in the first quarter of 2020.
This may make it more difficult for us to complete corporate transactions deemed advisable by our board of directors. Under U.S. law, generally only majority shareholder approval is required to amend the certificate of incorporation or to approve other significant transactions. • In the United Kingdom, takeovers may be structured as takeover offers or as schemes of arrangement.
This may make it more difficult for us to complete corporate transactions deemed advisable by our board of directors. Under U.S. law, generally only majority shareholder approval is required to amend the certificate of incorporation or to approve other significant transactions. • In the UK, takeovers may be structured as takeover offers or as schemes of arrangement.
In these countries, pricing negotiations with individual governmental authorities can take six to 12 months or longer after the receipt of regulatory marketing approval for a product, and is not always successful.
In these countries, pricing negotiations with individual governmental authorities can take six to 12 months or longer after the receipt of regulatory marketing approval for a product, and these negotiations are not always successful.
Such conduct also could be grounds for CMS to terminate our Medicaid drug rebate agreement, in which case federal payments may not be available under Medicaid or Medicare Part B for our covered outpatient drugs.
Such conduct also could be grounds for CMS to terminate our Medicaid drug rebate agreement, in which case federal payments may not be available under Medicaid or Medicare Part D for our covered outpatient drugs.
These parties exercise a substantial amount of bargaining power over us given their control over large segments of the market for VASCEPA. This bargaining power has led us to bear increasingly higher discounts in the sale of VASCEPA.
These parties exercise a substantial amount of bargaining power over us given their control over large segments of the market for VASCEPA. This bargaining power has required us to bear increasingly higher discounts in the sale of VASCEPA.
If our suppliers were unable to supply us with adequate volumes of active pharmaceutical ingredient, or API, (drug substance) or encapsulated bulk product (drug product), it would have a material adverse effect on our ability to continue to commercialize VASCEPA. We have contractual freedom to source the API for VASCEPA and to procure other services supporting our supply chain.
If our suppliers were unable to supply us with adequate volumes of API (drug substance) or encapsulated bulk product (drug product), it would have a material adverse effect on our ability to continue to commercialize VASCEPA. We have contractual freedom to source the API for VASCEPA and to procure other services supporting our supply chain.
Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and shares, we believe that we will not be classified as a PFIC for the taxable year ended December 31, 2022, and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.
Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and ordinary shares, we believe that we will not be classified as a PFIC for the taxable year ended December 31, 2023, and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.
For example, on November 30, 2020 we filed a patent infringement lawsuit against Hikma for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified cardiovascular risk.
On November 30, 2020, we filed a patent infringement lawsuit against Hikma for making, selling, offering to sell and importing generic icosapent ethyl capsules in and into the United States in a manner that we allege has induced the infringement of patents covering the use of VASCEPA to reduce specified CV risk.
We may not achieve profitability on a sustained basis in the near term due to high costs associated with, for example, our expanded commercialization efforts in the United States and our expected commercialization efforts in Europe.
We may not achieve profitability on a sustained basis in the near term due to high costs associated with, for example, our commercialization efforts in the United States and Europe.
The STRENGTH trial of an omega-3 mixture studied at 4-grams per day also failed to demonstrate cardiovascular benefit. 37 As generic company competitors seek to compete with copies of VASCEPA in the United States and elsewhere we could face additional challenges to our patents and additional patent litigation.
The STRENGTH trial of an omega-3 mixture studied at 4-grams per day also failed to demonstrate cardiovascular benefit. As generic competitors seek to compete with VASCEPA in the United States and elsewhere we could face additional challenges to our patents and additional patent litigation.
These incentives could also lead to suits that we have mischaracterized a competitor’s product in the marketplace and we may, as a result, be sued for alleged damages to our competitors. Such lawsuits, whether with or without merit, are typically time-consuming and costly to defend. Such suits may also result in related shareholder lawsuits, which are also costly to defend.
These incentives could also lead to suits that we have mischaracterized a competitor’s product in the marketplace and we may, as a result, be sued for alleged damages to our competitors. Such lawsuits, whether with or without merit, are typically time consuming and costly to defend.
FDA, other regulatory agencies and industry organizations strictly regulate the promotional claims that may be made about prescription products and promotional efforts such as speaker programs.
The U.S. FDA, other regulatory agencies and industry organizations strictly regulate the promotional claims that may be made about prescription products and promotional efforts such as speaker programs.
In April 2021, Dr. Reddy’s filed a complaint against us in the United States District Court District of New Jersey (case no. 2:21-cv-10309) alleging various antitrust violations stemming from alleged anticompetitive practices related to the supply of active pharmaceutical ingredient of VASCEPA. Damages sought include recovery for alleged economic harm to Dr.
In April 2021, Dr. Reddy’s filed a complaint against us in the United States District Court District of New Jersey (case no. 2:21-cv-10309) alleging various antitrust violations stemming from alleged anticompetitive practices related to the supply of API of VASCEPA. Damages sought include recovery for alleged economic harm to Dr.
Additional data or related interpretations that are generated or arise over time related to REDUCE-IT might not meet expectations, and the perception of REDUCE-IT results and VASCEPA revenue potential may suffer and our stock price may decline. While the U.S.
Additional data or related interpretations that are generated or arise over time related to REDUCE-IT might not meet expectations, and the perception of REDUCE-IT results and VASCEPA revenue potential may suffer and our stock price may decline.
The continuing efforts of the U.S. and foreign governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce healthcare costs may adversely affect our ability to set prices for our products which we believe are fair, and our ability to generate revenues and achieve and maintain 41 profitability. Refer to Item 1.
The continuing efforts of the U.S. and foreign governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce healthcare costs may adversely affect our ability to set prices for our products which we believe are fair, and our ability to generate revenues and achieve and maintain profitability.
The Arbitration Board process concluded without an agreement in November 2022 and although we plan to resubmit a pricing and reimbursement dossier with new data in Germany once we have a new dossier ready, we may be unable to resume commercial operations in Germany.
The Arbitration Board process concluded without an agreement in November 2022 and although we plan to resubmit a pricing and reimbursement dossier with new data in Germany, we may be unable to resume commercial operations in Germany.
FDA-approved labeling and the related perception thereof; • sufficient third-party coverage or reimbursement for VASCEPA and its prescribed uses, on-label and off-label; • natural disasters, including pandemics such as the COVID-19 pandemic, international conflicts, and political unrest which could inhibit our ability to promote VASCEPA regionally and which could negatively affect product demand by creating obstacles for patients to seek treatment and fill prescriptions; • new policies or laws affecting VASCEPA sales, such as state and federal efforts to affect drug pricing and provide or remove healthcare coverage that includes reimbursement for prescription drugs; and • the actual and perceived efficacy of the product and the prevalence and severity of any side effects and warnings in VASCEPA’s approved labeling internationally.
FDA-approved labeling and the related perception thereof; • sufficient third-party coverage or reimbursement for VASCEPA and its prescribed uses, on-label and off-label; • natural disasters, pandemics, international conflicts and political unrest, all of which could negatively impact our supply chain or inhibit our ability to promote VASCEPA regionally and which could negatively affect product demand by creating obstacles for patients to seek treatment and fill prescriptions; • new policies or laws affecting VASCEPA sales, such as state and federal efforts to affect drug pricing and provide or remove healthcare coverage that includes reimbursement for prescription drugs; and • the actual and perceived efficacy of the product and the prevalence and severity of any side effects and warnings in VASCEPA’s approved labeling internationally.
The process of obtaining regulatory approvals is lengthy and expensive and the issuance of such approvals is uncertain. 45 The commencement and rate of completion of clinical trials and the timing of obtaining marketing approval from regulatory authorities may be delayed by many factors, including, among others: • the lack of efficacy during clinical trials; • the inability to manufacture sufficient quantities of qualified materials under cGMPs for use in clinical trials; • slower than expected rates of patient recruitment; • the inability to observe patients adequately after treatment; • changes in regulatory requirements for clinical trials or preclinical studies; • the emergence of unforeseen safety issues in clinical trials or preclinical studies; • delay, suspension, or termination of a trial by the institutional review board responsible for overseeing the study at a particular study site; • unanticipated changes to the requirements imposed by regulatory authorities on the extent, nature or timing of studies to be conducted on quality, safety and efficacy; • compliance with laws and regulations related to patient data privacy; • government or regulatory delays or “clinical holds” requiring suspension or termination of a trial; and • political instability or other social or government protocols affecting our clinical trial sites.
The commencement and rate of completion of clinical trials and the timing of obtaining marketing approval from regulatory authorities may be delayed by many factors, including, among others: • the lack of efficacy during clinical trials; • the inability to manufacture sufficient quantities of qualified materials under cGMPs for use in clinical trials; 41 • slower than expected rates of patient recruitment; • the inability to observe patients adequately after treatment; • changes in regulatory requirements for clinical trials or preclinical studies; • the emergence of unforeseen safety issues in clinical trials or preclinical studies; • delay, suspension, or termination of a trial by the institutional review board responsible for overseeing the study at a particular study site; • unanticipated changes to the requirements imposed by regulatory authorities on the extent, nature or timing of studies to be conducted on quality, safety and efficacy; • compliance with laws and regulations related to patient data privacy; • government or regulatory delays or “clinical holds” requiring suspension or termination of a trial; and • political instability or other social or government protocols affecting our clinical trial sites.
If we are unsuccessful in consummating any such transaction or collaboration, we may be required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.
If we are unsuccessful in consummating any such transaction or collaboration, we may be required to re-evaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.
Following the patent litigation rulings against us, generic versions of VASCEPA began launching in the United States in November 2020, and several generic versions are currently available including for both the 0.5-gram and 1-gram capsules, and we expect that VASCEPA could face more competition from generic companies in the United States.
Following the ANDA litigation rulings against the Company, generic versions of VASCEPA began launching in the United States in November 2020, and several generic versions are currently available, including for both the 0.5-gram and 1-gram capsules, and we expect that VASCEPA could face more competition from generic companies in the United States.
The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including if we are unable to secure favorable product reimbursement levels, which can vary from country to country. If we are unable to realize product reimbursement rates at reasonable levels, or at all, patient access to VASCEPA may be limited.
The commercial value of VASCEPA outside the United States may be smaller than we anticipate, including if we are unable to secure favorable product pricing and reimbursement levels, which vary from country to country. If we are unable to realize product reimbursement rates at reasonable price levels, or at all, patient access to VASCEPA may be limited.
This process is conducted on a country-by-country basis and is time-consuming and complex, and, even though the EC approved the marketing authorization for VAZKEPA in March 2021, and we have received positive national pricing and reimbursement decisions in England and Wales, Sweden and Finland, there is no guarantee that we will be able to negotiate and obtain further reimbursement and pricing terms on favorable terms, or at all, in the countries where we are pursuing commercialization.
This process is conducted on a country-by-country basis and is time consuming and complex, and, even though the EC approved the marketing authorization for VAZKEPA in March 2021, and we have received positive national pricing and reimbursement decisions in various countries, there is no guarantee that we will be able to negotiate and obtain further reimbursement and pricing terms on favorable terms, or at all, in the other countries where we are pursuing commercialization.
Reddy's, Apotex and Teva, who have greater resources than us, and with the potential for further generic versions being launched, it may not be viable for us to continue to invest in market education to grow the market and our ability to maintain current promotional efforts and attract favorable commercial terms in several aspects of our business will likely be adversely affected as we face increased generic competition, or if we launch our own generic version of VASCEPA.
Reddy's, Apotex and Teva, all of which have greater resources than us, and with the potential for further generic versions being launched possibly in the near term, it may not be viable for us to continue to invest in 33 market education to grow the market and our ability to maintain current promotional efforts and attract favorable commercial terms in several aspects of our business will likely be adversely affected as we face increased generic competition, or if we launch our own generic version of VASCEPA.
If healthcare providers or patients favor dietary supplements over prescribing VASCEPA, we may be constrained in how we price our product or VASCEPA’s market acceptance may be less than expected, which would have a negative impact on our revenues and results of operations. 40 Our products and marketing efforts are subject to extensive post-approval government regulation.
If healthcare providers or patients favor dietary supplements over prescribing VASCEPA, we may be constrained in how we price VASCEPA or VASCEPA’s market acceptance may be less than expected, which would have a negative impact on our revenues and results of operations. Our products and marketing efforts are subject to extensive post-approval government regulation. Once a product candidate receives U.S.
As a result, the lack of alternative markets and products we develop could constrain our ability to generate revenues and achieve profitability. In the United States, we face increasing competition from generic drug companies in the near term and our revenues and results of operations could continue to be materially and adversely affected.
As a result, the lack of alternative markets and products we develop could constrain our ability to generate revenues and achieve profitability. In the United States, we compete with, and may face increasing competition from, generic drug companies and our revenues and results of operations could continue to be materially and adversely affected.
Risks Related to Our Financial Position and Capital Requirements We have a history of operating losses and anticipate that we will incur continued losses for an indefinite period of time. We have not yet reached sustained profitability. For the fiscal year ended December 31, 2022 and 2020, we reported net losses of approximately $105.8 million and $18.0 million, respectively.
Risks Related to Our Financial Position and Capital Requirements We have a history of operating losses and anticipate that we will incur continued losses for an indefinite period of time. We have not yet reached sustained profitability. For the fiscal year ended December 31, 2023 and 2022, we reported net losses of approximately $59.1 million and $105.8 million, respectively.
If our promotional activities or other operations are found to be in violation of any law or governmental regulation through existing or new interpretations, we may be subject to prolonged litigation, penalties, including civil and criminal penalties, damages, fines and the curtailment or restructuring of our operations.
If our promotional activities or other operations are found to be in violation of any law or governmental regulation through existing or new interpretations or as a result of the findings of the Investigations, we may be subject to prolonged litigation, penalties, including civil and criminal penalties, damages, fines and the curtailment or restructuring of our operations.
Changes in tax laws (including in response to the COVID-19 pandemic) or tax rulings, or changes in interpretations of existing laws, could cause us to be subject to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, digital tax, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations.
Changes in tax laws or tax rulings, or changes in interpretations of existing laws, could cause us to be subject to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, digital tax, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations.
Ongoing trials of moderate-to-high doses of VASCEPA and icosapent ethyl, or a similar eicosapentaenoic acid product could render new or adverse information on the effects of VASCEPA and its commercial and regulatory prospects.
Analysis of data from trials of moderate-to-high doses of VASCEPA and icosapent ethyl, or a similar eicosapentaenoic acid product, could render new or adverse information on the effects of VASCEPA and its commercial and regulatory prospects.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeOn January 20, 2023, we entered into a sublease agreement to sublease 50,000 square feet of the leased 67,747 square feet of office space in Bridgewater, New Jersey. The sublease commences on February 1, 2023 and terminates as of the date of the head lease.
Biggest changeOn May 2, 2023, we entered into an agreement to lease additional office space at our Dublin office, effective June 1, 2023 which terminates on September 30, 2024, and can be extended automatically for successive two year periods. Effective February 5, 2019, we entered into a lease agreement for approximately 67,747 square feet of office space in Bridgewater, New Jersey.
P roperties The following table lists the location, use and ownership interest of our principal properties as of March 1, 2023: Location Use Ownership Size (sq. ft.) Dublin, Ireland Offices Leased 1,302 Bridgewater, New Jersey, USA Offices Leased 67,747 Zug, Switzerland Offices Leased 4,511 On September 13, 2022, we entered into a License Agreement for office space in Dublin, Ireland effective October 1, 2022 which terminates on September 30, 2024 and can be extended automatically for successive two year periods.
P roperties The following table lists the location, use and ownership interest of our principal properties as of February 29, 2024: Location Use Ownership Size (sq. ft.) Dublin, Ireland Offices Leased 2,674 Bridgewater, New Jersey, USA Offices Leased 67,747 Zug, Switzerland Offices Leased 4,511 On September 13, 2022, we entered into a license agreement for office space in Dublin, Ireland, effective October 1, 2022 which terminates on September 30, 2024, and can be extended automatically for successive two-year periods.
On October 10, 2021, we entered into a lease agreement for approximately 4,511 square feet of office space in Zug, Switzerland. The lease commenced on February 1, 2022 for a 5-year period, with one five-year renewal option.
The sublease commenced on February 1, 2023 and terminates as of the date of the head lease. On October 10, 2021, we entered into a lease agreement for approximately 4,511 square feet of office space in Zug, Switzerland. The lease commenced on February 1, 2022 for a five-year period, with one five-year renewal option.
Effective February 5, 2019, we entered into a lease agreement for approximately 67,747 square feet of office space in Bridgewater, New Jersey. The lease commenced on August 15, 2019, for an 11-year period, with two five-year renewal options.
The lease commenced on August 15, 2019, for an 11-year period, with two five-year renewal options. On January 20, 2023, we entered into a sublease agreement to sublease 50,000 square feet of the leased 67,747 square feet of office space in Bridgewater, New Jersey.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRefer to Note—7 Commitments and Contingencies to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for further details on our legal proceedings. Item 4. Mine Safe ty Disclosures Not applicable. 64 PART II
Biggest changeRefer to Note—7 Commitments and Contingencies to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for further details on our legal proceedings. Item 4. Mine Safe ty Disclosures Not applicable. 59 PART II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 64 PART II Item 5. Market For Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 65 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 74 Item 7A. Quantitative and Qualitative Disclosures about Market Risk 86
Biggest changeItem 4. Mine Safety Disclosures 59 PART II Item 5. Market For Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 60 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 69 Item 7A. Quantitative and Qualitative Disclosures about Market Risk 81

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeCompany/Market/Peer Company 12/31/2018 12/31/2019 12/31/2020 12/31/2021 12/31/2022 Amarin Corporation PLC $ 330.17 $ 537.41 $ 124.94 $ 84.04 $ 30.17 NASDAQ Composite Index $ 95.38 $ 130.47 $ 185.48 $ 226.63 $ 151.61 NASDAQ Biotechnology Index $ 88.94 $ 113.68 $ 146.04 $ 140.88 $ 125.52 Information about Our Equity Compensation Plans Information regarding our equity compensation plans is incorporated by reference in Item 12 of Part III of this Annual Report on Form 10-K.
Biggest changeAlso included during this five-year period is the substantial negative impact on the price of Amarin’s ADSs in 2020 following the loss of the Company’s patent litigation and subsequent appeal. 60 Company/Market/Peer Company 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 Amarin Corporation PLC $ 163.26 $ 37.95 $ 25.53 $ 9.17 $ 6.59 NASDAQ Composite Index $ 133.65 $ 190.01 $ 232.16 $ 155.32 $ 222.76 NASDAQ Biotechnology Index $ 118.20 $ 151.85 $ 146.49 $ 130.51 $ 135.39 Information about Our Equity Compensation Plans Information regarding our equity compensation plans is incorporated by reference in Item 12 of Part III of this Annual Report on Form 10-K.
Holder means a holder of shares or ADSs evidenced by ADRs that (i) beneficially owns the shares or ADSs registered in their name; (ii) is resident in the United States for the purposes of the Ireland-United States Double Taxation Convention, or the Treaty; (iii) in the case of an individual holder, is not also resident or ordinarily resident in Ireland for Irish tax purposes; (iv) in the case of a corporate holder, is not a resident in Ireland for Irish tax purposes and is not ultimately controlled by persons resident in Ireland; and (v) is not engaged in any trade or business and does not 71 perform independent personal services through a permanent establishment or fixed base in Ireland; and (vi) is a qualified person as defined in Article 23 of the Treaty.
Holder means a holder of shares or ADSs evidenced by ADRs that (i) beneficially owns the shares or ADSs registered in their name, (ii) is resident in the United States for the purposes of the Ireland-United States Double Taxation Convention, or the Treaty, (iii) in the case of an individual holder, is not also resident or ordinarily resident in Ireland for Irish tax purposes, (iv) in the case of a corporate holder, is not a resident in Ireland for Irish tax purposes and is not ultimately controlled by persons resident in Ireland, and (v) is not engaged in any trade or business and does not perform independent personal services through a permanent establishment or fixed base in Ireland, and (vi) is a qualified person as defined in Article 23 of the Treaty.
Tax Considerations The following is a summary of certain U.S. federal income tax considerations with respect to the ownership and disposition of ordinary shares or ADSs by a U.S. Holder (as defined below). This summary applies to you only if you hold ordinary shares or ADSs 66 as a capital asset. This summary is based upon the U.S.
Tax Considerations The following is a summary of certain U.S. federal income tax considerations with respect to the ownership and disposition of ordinary shares or ADSs by a U.S. Holder (as defined below). This summary applies to you only if you hold ordinary shares or ADSs as a capital asset. This summary is based upon the U.S.
Holders, provided that certain significant holding period and other requirements are met. Any dividends that are qualified dividend income will generally be taxed at preferential rates to a non-corporate U.S. Holder. Any dividends paid to a corporate holder will not be eligible for the dividends received deduction. U.S.
Holders, provided that certain significant holding period and other requirements are met. Any dividends that are qualified dividend income will 62 generally be taxed at preferential rates to a non-corporate U.S. Holder. Any dividends paid to a corporate holder will not be eligible for the dividends received deduction. U.S.
Rules for Lower-Tier PFIC Subsidiaries. Special adverse rules apply to U.S. Holders of ordinary shares or ADSs for any year in which we are a PFIC and have a non-U.S. subsidiary that is also a PFIC, or a lower-tier PFIC. If we are or become a PFIC and a U.S.
Rules for Lower-Tier PFIC Subsidiaries. Special adverse rules apply to U.S. Holders of ordinary shares or ADSs for any year in which we are a PFIC and have a non-U.S. subsidiary that is also a PFIC, or a lower-tier PFIC. If we are or become a PFIC and a 64 U.S.
For Irish taxation purposes, and for the purposes of the Treaty, U.S. Holders of ADSs will be treated as the owners of the shares represented by such ADSs. The following discussion is limited to the tax consequences of ownership and disposition of shares or ADSs.
For Irish taxation purposes, and for the purposes of the Treaty, U.S. Holders of ADSs will be treated as the owners of the shares represented by such ADSs. 66 The following discussion is limited to the tax consequences of ownership and disposition of shares or ADSs.
Holder’s holding period, any gain recognized in the year of the election will be treated like an excess distribution (as 69 described above).
Holder’s holding period, any gain recognized in the year of the election will be treated like an excess distribution (as described above).
The person who receives the gift or inheritance is generally accountable for any CAT due. 72 Irish stamp duty No Irish stamp duty should arise on the issue or transfer for cash of shares or ADSs on the basis that such a transfer does not relate to stocks or marketable securities of an Irish registered company.
The person who receives the gift or inheritance is generally accountable for any CAT due. Irish stamp duty No Irish stamp duty should arise on the issue or transfer for cash of shares or ADSs on the basis that such a transfer does not relate to stocks or marketable securities of an Irish registered company. 67
The following graph compares the cumulative 5-year return provided to shareholders of our ADSs relative to the cumulative total returns of the NASDAQ Composite Index and the NASDAQ Biotechnology Index. We believe these indices are the most appropriate indices against which the total shareholder return of Amarin should be measured.
The following graph compares the cumulative five-year return provided to shareholders of our ADSs relative to the cumulative total returns of the NASDAQ Composite Index and the NASDAQ Biotechnology Index. We believe these indices are the most appropriate indices against which the total shareholder return of Amarin should be measured.
Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and ordinary shares, we believe that we will not be classified as a 68 PFIC for the taxable year ended December 31, 2022, and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.
Based on certain estimates of our gross income and gross assets, the latter determined by reference to the expected value of our ADSs and ordinary shares, we believe that we will not be classified as a PFIC for the taxable year ended December 31, 2023, and we do not expect to be treated as a PFIC in any future taxable year for the foreseeable future.
Included in this 5-year time period is the substantial positive impact on the price of Amarin’s ADSs in 2018 following presentation and publication of positive REDUCE-IT results and, in late 2019, following approval by the FDA of a new indication and 65 label expansion for VASCEPA to reduce cardiovascular risk.
Included in this five-year time period is the substantial positive impact on the price of Amarin’s ADSs in 2018 following presentation and publication of positive REDUCE-IT results and, in late 2019, following approval by the FDA of a new indication and label expansion for VASCEPA to reduce cardiovascular risk.
The NASDAQ Biotechnology Index has been selected because it is an index of U.S. quoted biotechnology and pharmaceutical companies. An investment of $100 (with reinvestment of all dividends) is assumed to have been made in our ADSs and in each of the indices on December 31, 2017, and its relative performance is tracked through December 31, 2022.
The NASDAQ Biotechnology Index has been selected because it is an index of U.S. quoted biotechnology and pharmaceutical companies. An investment of $100 (with reinvestment of all dividends) is assumed to have been made in our ADSs and in each of the indices on December 31, 2018, and its relative performance is tracked through December 31, 2023.
Holders should assume that any distribution by us with respect to the ordinary shares and ADSs will constitute ordinary dividend income. 67 Subject to the discussion under “—Passive Foreign Investment Company,” below, as long as our ordinary shares or ADSs (as applicable) are treated as publicly traded on an established securities market, or we are eligible for the benefits of the U.S.-Irish Tax Treaty, any distributions treated as dividends will generally be qualified dividend income in the hands of non-corporate U.S.
Subject to the discussion under “—Passive Foreign Investment Company,” below, as long as our ordinary shares or ADSs (as applicable) are treated as publicly traded on an established securities market, or we are eligible for the benefits of the U.S.-Irish Tax Treaty, any distributions treated as dividends will generally be qualified dividend income in the hands of non-corporate U.S.
If we are a PFIC for any year, subject to the discussion of QEF (as defined herein) and mark-to-market elections below, a U.S. taxpayer who disposes or is deemed to dispose of an ordinary share or ADS at a gain or who receives a distribution treated as an “excess distribution” on an ordinary share or ADS generally would be required to allocate such gain and distribution ratably to each day in the U.S. taxpayer’s holding period for the ordinary share or ADS in question.
“Passive income” includes, for example, dividends, interest, certain rents and royalties, certain gains from the sale of stock and securities, and certain gains from commodities transactions. 63 If we are a PFIC for any year, subject to the discussion of QEF (as defined herein) and mark-to-market elections below, a U.S. taxpayer who disposes or is deemed to dispose of an ordinary share or ADS at a gain or who receives a distribution treated as an “excess distribution” on an ordinary share or ADS generally would be required to allocate such gain and distribution ratably to each day in the U.S. taxpayer’s holding period for the ordinary share or ADS in question.
Capital gains If you are not resident in the United Kingdom, or UK, for UK tax purposes, you will not be liable for UK tax on capital gains realized or accrued on the sale or other disposition of ordinary shares or ADSs unless the ordinary shares or ADSs are held in connection with your trade carried on in the UK through a branch or agency and the ordinary shares or ADSs are or have been used, held or acquired for the purposes of such trade or such branch or agency.
Each shareholder should however seek individual tax advice as specific rules may apply in certain circumstances. 65 Capital gains If you are not resident in the United Kingdom, or UK, for UK tax purposes, you will not be liable for UK tax on capital gains realized or accrued on the sale or other disposition of ordinary shares or ADSs unless the ordinary shares or ADSs are held in connection with your trade carried on in the UK through a branch or agency and the ordinary shares or ADSs are or have been used, held or acquired for the purposes of such trade or such branch or agency.
The following table sets forth the high and low prices for our ADSs in each of the quarters over the past two fiscal years, as quoted on The NASDAQ Global Market under the symbol “AMRN.” Common Stock Price Fiscal 2022 Fiscal 2021 High Low High Low First Quarter $ 3.82 $ 2.76 $ 9.25 $ 4.80 Second Quarter $ 3.74 $ 1.11 $ 6.58 $ 4.16 Third Quarter $ 1.71 $ 1.04 $ 5.97 $ 3.84 Fourth Quarter $ 1.38 $ 1.06 $ 5.24 $ 3.11 Shareholders As of January 31, 2023, there were approximately 375 holders of record of our ordinary shares.
The following table sets forth the high and low prices for our ADSs in each of the quarters over the past two fiscal years, as quoted on The NASDAQ Global Market under the symbol “AMRN.” Common Stock Price Fiscal 2023 Fiscal 2022 High Low High Low First Quarter $ 2.23 $ 1.15 $ 3.82 $ 2.76 Second Quarter $ 1.50 $ 1.10 $ 3.74 $ 1.11 Third Quarter $ 1.49 $ 0.84 $ 1.71 $ 1.04 Fourth Quarter $ 0.93 $ 0.65 $ 1.38 $ 1.06 Shareholders As of January 31, 2024, there were approximately 350 holders of record of our ordinary shares.
Holders should consult their own tax advisors regarding information reporting and potential back up withholdings. 70 Certain Material UK Tax Considerations The following discussion is limited to an overview of the tax consequences of ownership and disposition of ordinary shares, or such shares represented by ADSs (those ordinary shares or ADSs deriving over 75% of their value otherwise than from United Kingdom land).
Certain Material UK Tax Considerations The following discussion is limited to an overview of the tax consequences of ownership and disposition of ordinary shares, or such shares represented by ADSs (those ordinary shares or ADSs deriving over 75% of their value otherwise than from United Kingdom land).
Internal Revenue Code of 1986, as amended, which is referred to herein as the Code, regulations promulgated under the Code and administrative rulings and judicial decisions as in effect on the date of this Annual Report on Form 10-K, all of which are subject to change and to differing interpretations, possibly with retroactive effect, which could result in U.S. federal income tax considerations different from those summarized below.
Internal Revenue Code of 1986, as amended, which is referred to herein as the Code, regulations promulgated under the Code and administrative rulings and judicial decisions as in effect on the date of this Annual Report on Form 10-K, all of which are subject to change and to differing interpretations, possibly with retroactive effect, which could result in U.S. federal income tax considerations different from those summarized below. 61 This summary is general in nature and does not address the effects of any state or local taxes, the tax consequences in jurisdictions other than the United States or any U.S. federal taxes other than income tax (such as estate or gift tax).
Recent Sales of Unregistered Securities None Issuer Purchases of Equity Securities Shares purchased in the fourth quarter of 2022 are as follows: Period Total Number of Shares Purchased (1) Average Price Paid per Share October 1 – 31, 2022 14,067 $ 1.09 November 1 – 30, 2022 9,794 1.17 December 1 – 31, 2022 131,885 1.20 Total 155,746 $ 1.19 (1) Represents shares withheld to satisfy tax withholding amounts due from employees related to the exercise or vesting of equity awards.
Recent Sales of Unregistered Securities None Issuer Purchases of Equity Securities Shares purchased in the fourth quarter of 2023 are as follows: Period Total Number of Shares Purchased (1) Average Price Paid per Share October 1 – 31, 2023 20,290 $ 0.87 November 1 – 30, 2023 35,343 0.74 December 1 – 31, 2023 161,456 0.86 Total 217,089 $ 0.84 (1) Represents shares withheld to satisfy tax withholding amounts due from employees related to the exercise or vesting of equity awards.
Removed
Also included during this 5-year period is the substantial negative impact on the price of Amarin’s ADSs in 2020 following the loss of the Company’s patent litigation and subsequent appeal.
Added
Share Repurchase Program On January 10, 2024, we announced plans to initiate a share repurchase program to purchase up to $50.0 million of our ordinary shares held in the form of ADSs. The implementation of the share repurchase program will require shareholder approval as well as UK High Court approval, as required under UK company law.
Removed
This summary is general in nature and does not address the effects of any state or local taxes, the tax consequences in jurisdictions other than the United States or any U.S. federal taxes other than income tax (such as estate or gift tax).
Added
Holders should assume that any distribution by us with respect to the ordinary shares and ADSs will constitute ordinary dividend income.
Removed
“Passive income” includes, for example, dividends, interest, certain rents and royalties, certain gains from the sale of stock and securities, and certain gains from commodities transactions.
Added
Holders should consult their own tax advisors regarding information reporting and potential back up withholdings.
Removed
Each shareholder should however seek individual tax advice as specific rules may apply in certain circumstances.

Item 7. Management's Discussion & Analysis

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

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Biggest changeBased on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, 30 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent 77 ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2022 as listed below: • In November 2022, the American Society of Preventive Cardiology published a clinical practice statement delineating key attributes that define the field of preventive cardiology, including that REDUCE-IT established that IPE reduced CV events among patients fasting TG 135 to 499 mg/dL and that results from REDUCE-IT have not been replicated in trials using mixed omega-3 fatty acids suggesting that the CV benefit is attributed to EPA. • In November 2022, NICE released its guidelines on lipid management, which included that IPE is recommended for patients with established CVD and elevated fasting TG and who are taking statins with LDL-C levels between 1.04 and 2.60 mmol/L, as per the REDUCE-IT results. • In December 2022, the Finnish Medical Association and the Finnish Association of Internists published updated guidelines on dyslipidemia treatment, including that IPE is indicated for patients on statin therapy who have elevated TG levels and are at particularly high risk for arterial disease. • In December 2022, the National Society of Cardiometabolic Medicine in China released its consensus statement on the role of omega-3 fatty acids in the prevention and treatment of CVD in Chinese patients.
Biggest changeBased on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, more than 40 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent ethyl in appropriate at-risk patients, including those statements which we were informed of by our global partners in Canada, China and the Middle East as well as guidelines which were newly received during the fourth quarter of 2023 as listed below: • In December 2023, the Hellenic Atherosclerosis Society published guidelines for the diagnosis and treatment of dyslipidemia.
Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma, and certain of their affiliates, several of our patents covering the MARINE indication were declared as invalid. As a result, the following generic versions of VASCEPA have obtained U.S.
Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma, and certain of their affiliates, several of our patents covering the MARINE indication were declared invalid. As a result, the following generic versions of VASCEPA have obtained U.S.
The evidence considered included the (i) historical taxable profitability of our U.S. operations, (ii) historical pre-tax book loss position, (iii) sources of future taxable income, giving weight to 81 sources according to the extent to which they can be objectively verified, (iv) the provisions of the Tax Cuts and Jobs Act enacted in 2017 and their impact on our future taxable income, and (v) the risks to our business related to the commercialization and development of VASCEPA.
The evidence considered included the (i) historical taxable profitability of our U.S. operations, (ii) historical pre-tax book loss position, (iii) sources of future taxable income, giving weight to sources according to the extent to which they can be objectively verified, (iv) the provisions of the Tax Cuts and Jobs Act enacted in 2017 and their impact on our future taxable income, and (v) the risks to our business related to the commercialization and development of VASCEPA.
Excess tax benefits and deficiencies that arise upon vesting or exercise of share-based payments are recognized as an income tax benefit and expense, respectively, in the consolidated statement of operations. Recent Accounting Pronouncements For a discussion of recent accounting pronouncements, see Note 2—Significant Accounting Policies in the accompanying Notes to Consolidated Financial Statements in this Annual Report on Form 10-K.
Excess tax benefits and deficiencies that arise upon vesting or exercise of share-based payments are recognized as an income tax benefit and expense, respectively, in the consolidated statement of operations. 76 Recent Accounting Pronouncements For a discussion of recent accounting pronouncements, see Note 2—Significant Accounting Policies in the accompanying Notes to Consolidated Financial Statements in this Annual Report on Form 10-K.
We estimate 80 our Product revenue, net by deducting from our gross product revenues (a) trade allowances, such as invoice discounts for prompt payment and distributor fees, (b) estimated government and private payor rebates, chargebacks and healthcare discounts, such as Medicaid reimbursements, (c) expected product returns and (d) estimated costs of incentives offered to certain indirect customers, including patients.
We estimate our Product revenue, net by deducting from our gross product revenues (a) trade allowances, such as invoice discounts for prompt payment and distributor fees, (b) estimated government and private payor rebates, chargebacks and healthcare discounts, such as Medicaid reimbursements, (c) expected product returns and (d) estimated costs of incentives offered to certain indirect customers, including patients.
When evaluating licensing arrangements, we perform the following steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when (or as) we satisfy each performance obligation.
When evaluating licensing arrangements, we perform the following steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when (or as) we satisfy each 75 performance obligation.
In addition, Research and development expenses include the cost to support current development efforts, costs of product supply received from suppliers when such receipt by us is prior to regulatory approval of the supplier, as well as license fees related to our strategic collaboration with Mochida. We expense research and development costs as incurred. Restructuring expense.
In addition, research and development expenses include the cost to support current development efforts, costs of product supply received from suppliers when such receipt by us is prior to regulatory approval of the supplier, as well as license fees related to our strategic collaboration with Mochida. We expense research and development costs as incurred. 74 Restructuring expense.
United States VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients and healthcare providers.
United States VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and retail and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients.
Selling, general and administrative expense consists primarily of salaries and other related costs, including stock-based compensation expense, for personnel in our sales, marketing, executive, business development, 79 finance and information technology functions. Other costs primarily include facility costs and professional fees for accounting, consulting and legal services. Research and development expense.
Selling, general and administrative expense consists primarily of salaries and other related costs, including stock-based compensation expense, for personnel in our sales, marketing, executive, business development, finance and information technology functions. Other costs primarily include facility costs and professional fees for accounting, consulting and legal services. Research and development expense.
We continuously evaluate all of our spending commitments and priorities and we plan to adjust our level of research and development activities based on various factors, including the impact of U.S. generic competition as well as timing of pricing reimbursements throughout Europe. Restructuring expense .
We continuously evaluate all of our spending commitments and priorities and we plan to adjust our level of research and development activities based on various factors, including the impact of U.S. generic competition as well as timing of pricing reimbursements throughout Europe. 79 Restructuring expense .
We also have multiple international API suppliers, encapsulators and packagers to support the commercialization of VASCEPA in geographies where the drug is approved outside the United States. Not all of our suppliers approved by the U.S. FDA are approved in every other geography.
We also have multiple international API suppliers, encapsulators and packagers to support the commercialization of VASCEPA in geographies where the drug is approved outside the 73 United States. Not all of our suppliers approved by the U.S. FDA are approved in every other geography.
FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication and commercially launched in 2013. On December 13, 2019, the U.S.
FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia, or the MARINE indication and we commercially launched in 2013. On December 13, 2019, the U.S.
Cost of goods sold includes the cost of API for VASCEPA as well as the associated costs for encapsulation, packaging, shipment, supply management, insurance and quality assurance, which revenue was recognized during the period. The cost of the API included in cost of goods sold reflects the average cost of API included in inventory.
Cost of goods sold includes the cost of API for VASCEPA on which revenue was recognized during the period, as well as the associated costs for encapsulation, packaging, shipment, supply management, insurance and quality assurance. The cost of the API included in cost of goods sold reflects the average cost of API included in inventory.
We disclaim any intent to update or announce revisions to any forward-looking statements to reflect actual events or developments, except as required by law. Except as otherwise indicated herein, all dates referred to in this Annual Report on Form 10-K represent periods or dates fixed with reference to our fiscal year ended December 31, 2022.
We disclaim any intent to update or announce revisions to any forward-looking statements to reflect actual events or developments, except as required by law. Except as otherwise indicated herein, all dates referred to in this Annual Report on Form 10-K represent periods or dates fixed with reference to our fiscal year ended December 31, 2023.
In applying guidance prescribed under ASC 740 and based on present evidence and conclusions around the realizability of deferred tax assets, we determined that any tax benefit related to the pretax losses generated for the year-ended December 31, 2022 and 2021, are not more likely than not to be realized.
In applying guidance prescribed under ASC 740 and based on present evidence and conclusions around the realizability of deferred tax assets, we determined that any tax benefit related to the pretax losses generated for the year-ended December 31, 2023 and 2022, are not more likely than not to be realized.
Also included are costs related to qualifying suppliers and costs associated with various other investigations, including other costs in collaboration with Mochida and pilot studies regarding VASCEPA. (5) Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to personnel supporting our research and development and regulatory functions.
Also included are costs related to qualifying suppliers and costs associated with various other activities, including other costs in collaboration with Mochida and pilot studies regarding VASCEPA. (5) Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to personnel supporting our research and development and regulatory functions.
Rest of World China In February 2015, we entered into an exclusive agreement with Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, to develop and commercialize VASCEPA capsules in what we refer to as the China Territory, consisting of the territories of Mainland China, Hong Kong, Macau and Taiwan.
China In February 2015, we entered into an exclusive agreement with Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, to develop and commercialize VASCEPA capsules in what we refer to as the China Territory, consisting of the territories of Mainland China, Hong Kong, Macau and Taiwan.
For a comparison of our results of operations and financial condition for fiscal years 2021 and 2020, see “Item 7—Management’s Discussion and Analysis of Financial Condition and Results of Operations” of our 2021 Annual Report on Form 10-K, filed with the SEC on March 1, 2022 .
For a comparison of our results of operations and financial condition for fiscal years 2022 and 2021, see “Item 7—Management’s Discussion and Analysis of Financial Condition and Results of Operations” of our 2022 Annual Report on Form 10-K, filed with the SEC on March 1, 2023 .
We receive payments from our customers based on billing schedules established in each contract. Up-front payments and fees are recorded as deferred revenue upon receipt or when due and may require deferral of revenue recognition to a future period until we perform our obligations under these arrangements. Amounts are recorded as accounts receivable when our right to consideration is unconditional.
We receive payments from our customers based on billing schedules established in each contract. Upfront payments and fees are recorded as deferred revenue upon receipt or when due and may require deferral of revenue recognition to a future period until we perform our obligations under these arrangements. Amounts are recorded as accounts receivable when our right to consideration is unconditional.
Effects of Inflation We believe the impact of inflation on operations has been minimal during the past three years. Results of Operations The discussion that follows includes a comparison of our results of operations and liquidity and capital resources for fiscal years 2022 and 2021.
Effects of Inflation We believe the impact of inflation on operations has been minimal during the past three years. Results of Operations The discussion that follows includes a comparison of our results of operations and liquidity and capital resources for fiscal years 2023 and 2022.
We rely on contract manufacturers in each step of our commercial and clinical product supply chain. These steps include active pharmaceutical ingredient, or API, manufacturing, encapsulation of the API, product packaging and supply-related logistics.
Commercial and Clinical Supply We manage the manufacturing and supply of VASCEPA and rely on contract manufacturers in each step of our commercial and clinical product supply chain. These steps include active pharmaceutical ingredient, or API, manufacturing, encapsulation of the API, product packaging and supply-related logistics.
When making our assessment about the realization of our deferred tax assets as of December 31, 2022, we considered all available evidence, placing particular weight on evidence that could be objectively verified.
When making our assessment about the realization of our deferred tax assets as of December 31, 2023, we considered all available evidence, placing particular weight on evidence that could be objectively verified.
Based on our assessment, we concluded that all of our net deferred tax assets are not more likely than not to be realizable as of both December 31, 2022 and 2021.
Based on our assessment, we concluded that all of our net deferred tax assets are not more likely than not to be realizable as of both December 31, 2023 and 2022.
Biologix obtained approval of VASCEPA under the MARINE and REDUCE-IT indications, and subsequently launched commercially, in the following countries: Country MARINE REDUCE-IT Launch Date Lebanon March 2018 August 2021 June 2018 United Arab Emirates July 2018 October 2021 February 2019 Qatar December 2019 April 2021 — Bahrain April 2021 April 2022 — Kuwait December 2021 — — Saudi Arabia March 2022 — — VASCEPA is under registration in additional countries in the MENA region.
Biologix obtained approval of VASCEPA under the MARINE and REDUCE-IT indications, and subsequently launched commercially, in the following countries: Country MARINE REDUCE-IT Launch Date Lebanon March 2018 August 2021 June 2018 United Arab Emirates July 2018 October 2021 February 2019 Qatar December 2019 April 2021 N/A Bahrain April 2021 April 2022 N/A Kuwait December 2021 March 2023 September 2023 Saudi Arabia March 2022 June 2023 September 2023 VASCEPA is under registration in additional countries in the MENA region.
We anticipate that quarterly net cash outflows in future periods will continue to be variable as a result of the timing of certain items, including our purchases of API, the generic competition in the United States and commercialization of VAZKEPA in Europe.
We anticipate that quarterly net cash outflows in future periods will continue to be variable as a result of the timing of certain items, including our purchases of API, the generic competition in the United States and pricing and reimbursement of VAZKEPA in Europe.
(4) Internal staffing, overhead and other research and development expenses primarily relate to the costs of our personnel employed to manage research, development and regulatory affairs activities and related overhead costs including consulting and other professional fees that are not allocated to specific projects, including costs associated with securing regulatory approvals for VAZKEPA in Europe as achieved in 2021 as well as further regulatory expansion in other countries throughout 2022.
(4) Internal staffing, overhead and other research and development expenses primarily relate to the costs of our personnel employed to manage research, development and regulatory affairs activities and related overhead costs including consulting and other professional fees that are not allocated to specific projects, including costs associated with securing and maintaining regulatory approvals for VAZKEPA in Europe as originally achieved in 2021, as well as regulatory expansion in other countries throughout 2023.
Since VASCEPA was made commercially available in 2013, more than twenty million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health. In 2020, following our unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr. Reddy’s Laboratories, Inc., or Dr.
Since VASCEPA was made commercially available in 2013, approximately 25 million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health. In 2020, following our unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr. Reddy’s Laboratories, Inc., or Dr.
In countries where 75 individual price reimbursement is allowed prior to national reimbursement, product can be made available on a patient by patient basis, while the national reimbursements negotiations are ongoing. In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic.
In certain countries, such as Denmark, individual patient reimbursement is allowed prior to national reimbursement. In countries where individual price reimbursement is allowed prior to national reimbursement, product can be made available on a patient by patient basis, while the national reimbursements negotiations are ongoing. In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic.
For the year ended December 31, 2022 we recorded $4.1 million of product revenue, net, to our collaboration partners compared to $1.7 million during the year ended December 31, 2021. 82 Despite the generic competition in the U.S., we remain confident that the global patient need for VASCEPA is high.
For the year ended December 31, 2023, we recorded $8.1 million of product revenue, net, to our collaboration partners compared to $4.1 million during the year ended December 31, 2022. Despite the generic competition in the U.S., we remain confident that the global patient need for VASCEPA is high.
Through the date of this Annual Report on Form 10-K, we have received and made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.
Through the date of this Annual Report, we have received and made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.
In 2022, we reviewed our contractual supplier purchase obligations and have taken steps to amend supplier agreements to align supply arrangements with current and future market demand, while we decrease our current inventory levels primarily related to North America approved inventory.
Beginning in 2022, we reviewed our contractual supplier purchase obligations and began taking steps to amend supplier agreements to align supply arrangements with current and future market demand, while we decrease our current inventory levels primarily related to North America approved inventory.
In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final NMPA review of the VASCEPA NDA was initiated with Edding expecting approval by the end of 2022.
In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final NMPA review of the VASCEPA NDA was initiated.
We have incurred annual operating losses since our inception and, as a result, we had an accumulated deficit of $1.5 billion as of December 31, 2022.
We have incurred annual operating losses since our inception and, as a result, we had an accumulated deficit of $1.6 billion as of December 31, 2023.
Revenues from sales to our international commercial partners are recognized when the commercial partners obtain control of our product upon delivery to the commercial partner.
Revenues from sales to our international commercial partners are recognized when the commercial partners obtain control of our product.
Excluding the restructuring inventory and inventory write-off, gross margin was 73% for the year ended December 31, 2022. The remaining decrease in gross margin is primarily as a result of a decrease in net selling price. Selling, General and Administrative Expense.
Excluding the restructuring inventory and inventory write-off charges, gross margin was 66% and 73% for the years ended December 31, 2023 and 2022, respectively. The remaining decrease in gross margin is primarily as a result of a decrease in net selling price. Selling, general and administrative expense.
FDA approval with labeling consistent with the MARINE indication and have entered the U.S. market with a 1-gram capsule: Company FDA MARINE Indication Approval Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 Teva Pharmaceuticals USA, Inc. September 2020 September 2022 (1) Apotex, Inc.
FDA approval with labeling consistent with the MARINE indication and have entered the U.S. market: Company FDA MARINE Indication Approval 1-gram Launch Date 0.5-gram Launch Date Hikma Pharmaceuticals USA Inc. May 2020 November 2020 March 2023 Dr. Reddy’s Laboratories, Inc. August 2020 June 2021 June 2023 Teva Pharmaceuticals USA, Inc. September 2020 January 2023 September 2022 Apotex, Inc.
In the year ended December 31, 2022, we incurred costs of $18.1 million in Cost of goods sold - restructuring inventory related to steps taken to amend supplier agreements to align supply arrangements with current and future market demand. Selling, general and administrative expense.
In the years ended December 31, 2023 and 2022, we incurred costs within Cost of goods sold - restructuring inventory related to steps taken to amend supplier agreements to align supply arrangements with current and future market demand. Selling, general and administrative expense.
Net interest income for the years ended December 31, 2022 and 2021 was $2.8 million and $1.1 million, respectively, an increase of $1.7 million, or 157%. The increase is primarily due to higher interest rates in the current year compared to the prior year. Other (expense) income, net .
The increase is primarily due to higher interest rates in the current year period compared to the prior year period. Other income (expense), net . Other income (expense), net, for the year ended December 31, 2023 and 2022 was income of $2.1 million and expense of $0.7 million, respectively, an increase of $2.8 million or 379%.
As of December 31, 2022, we had inventory $392.4 million, of which 90% is inventory approved for use in North America. We continue to negotiate with our contract suppliers to align our supply arrangements with current and future global market demand. Financial Operations Overview Product revenue, net.
As of December 31, 2023, we had inventory of $336.2 million, of which 80% is inventory approved for use in North America. We continue to negotiate with our contract suppliers to align our supply arrangements with current and future global market demand. Financial Operations Overview Product revenue, net.
We have completed the first year of a three year plan to submit and obtain regulatory approval in 20 additional countries in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.
Other We completed the second year of a three-year plan to submit and obtain regulatory approval in 20 or more additional countries and regions in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA.
The decrease is primarily due to the decrease in U.S. field force as well as the reversal of expense associated with certain performance-based awards as it was no longer deemed probable that the performance criteria for vesting would be achieved within the required timeframe.
The decrease is due to the reversal of expense associated with certain performance-based awards as it was no longer deemed probable that the performance criteria for vesting would be achieved within the required timeframe.
We believe that our cash and cash equivalents and our short-term investments will be sufficient to fund our projected operations for at least twelve months from the issuance date of our audited consolidated financial statements included elsewhere within this Annual Report and is adequate to support continued operations based on our current plans.
We believe that our cash and cash equivalents and our short-term investments will be sufficient to fund our projected operations, including the share repurchase program, for at least one year from the issuance date of our audited consolidated financial statements included elsewhere in this Annual Report and is adequate to support continued operations based on our current plans.
Through the date of this Annual Report on Form 10-K, we have filed for regulatory review in 10 countries and have received approval in seven countries outside of the United States and European Medicines Agency, or EMA, regulatory approval authority, including in Switzerland, Australia and New Zealand, under the REDUCE-IT indication.
Through the date of this Annual Report, we have filed for regulatory review in 20 countries and regions and have received approval in 13 countries and regions outside of the United States and European Medicines Agency, or EMA, regulatory approval authority, including in Switzerland, Australia, New Zealand and Israel, under the REDUCE-IT indication.
Other (expense) income, net, consists primarily of foreign exchange losses and gains. Income tax provision. Income tax provision, deferred tax assets and liabilities, and reserves for unrecognized tax benefits reflect management’s best assessment of estimated future taxes to be paid. We are subject to income taxes in both the United States and foreign jurisdictions.
Income tax provision. Income tax provision, deferred tax assets and liabilities, and reserves for unrecognized tax benefits reflect management’s best assessment of estimated future taxes to be paid. We are subject to income taxes in both the United States and foreign jurisdictions.
A hypothetical 5% change in estimated aggregate bottles of channel inventory would result in a change of less than 1% in net product revenues reported during each of the three and twelve months ended December 31, 2022 and 2021.
A hypothetical 5% change in estimated aggregate bottles of channel inventory would result in a change of less than 1% in net product revenues reported during the years ended December 31, 2023 and 2022.
These suppliers compete with each other based on cost, consistent quality, capacity, timely delivery and other factors. In the future, we may see the average cost of supply change based on numerous potential factors including increased volume purchases, continued improvement in manufacturing efficiency, the mix of purchases made among suppliers, currency exchange rates and other factors.
In the future, we may see the average cost of supply change based on numerous potential factors including increased volume purchases, continued improvement in manufacturing efficiency, the mix of purchases made among suppliers, currency exchange rates and other factors.
This average cost reflects the actual purchase price of VASCEPA API. During 2022, as part of our cost reduction plan, we have taken steps to amend supplier agreements to align supply arrangements with current and future demand resulting in a $18.1 million charge, which was recorded as Cost of goods sold - restructuring inventory.
This average cost reflects the actual purchase price of VASCEPA API. During 2023 and 2022, we have taken steps to amend supplier agreements to align supply arrangements with current and future demand resulting in charges of $39.2 million and $18.1 million, respectively, which were recorded as cost of goods sold - restructuring inventory.
Restructuring expense for the years ended December 31, 2022 and 2021 was $13.5 million and $13.7, respectively, a decrease of $0.2 million or 1%.
Restructuring expense for the years ended December 31, 2023 and 2022 was $11.0 million and $13.5 million, respectively, a decrease of $2.6 million, or 19%.
In April 2022, HLS completed negotiations with Canada’s pan-Canadian Pharmaceutical Alliance for the terms and conditions under which VASCEPA would qualify for public market reimbursement in Canada.
In January 2020, HLS obtained regulatory exclusivity designation and launched commercially in February 2020. In April 2022, HLS completed negotiations with Canada’s pan-Canadian Pharmaceutical Alliance for the terms and conditions under which VASCEPA would qualify for public market reimbursement in Canada.
Comparison of Fiscal Years Ended December 31, 2022 and December 31, 2021 Total revenue, net. We recorded total revenue, net, of $369.2 million and $583.2 million during the years ended December 31, 2022 and 2021, respectively, a decrease of $214.0 million, or 37%. Total revenue, net consists primarily of revenue from the sale of VASCEPA in the United States.
Comparison of Fiscal Years Ended December 31, 2023 and December 31, 2022 Total revenue, net. We recorded total revenue, net, of $306.9 million and $369.2 million during the years ended December 31, 2023 and 2022, respectively, a decrease of $62.3 million, or 17%. Total revenue, net consists primarily of revenue from the sale of VASCEPA in the United States.
We currently anticipate API average cost in 2023 to be similar to or modestly lower than 2022. The average cost may be variable from period to period depending upon the timing and quantity of API purchased from each supplier. Our gross margin on product sales for the years ended December 31, 2022 and 2021 was 65% and 79%, respectively.
The average cost may be variable from period to period depending upon the timing and quantity of API purchased from each supplier. Our overall gross margin on product sales for the years ended December 31, 2023 and 2022 was 50% and 65%, respectively.
Licensing and royalty revenue relates to the recognition of amounts received in connection with the following VASCEPA licensing agreements: • Edding – a $15.0 million up-front payment received in February 2015 and a $1.0 million milestone payment achieved in March 2016. • HLS – a $5.0 million up-front payment which was received upon closing of the agreement in September 2017, a $2.5 million milestone payment that was received following achievement of the REDUCE-IT trial primary endpoint in September 2018, a $2.5 million milestone payment that was received following U.S.
Licensing and royalty revenue relates to the recognition of amounts received in connection with the following VASCEPA licensing agreements: • Edding – a $15.0 million upfront payment received in February 2015, a $1.0 million milestone payment achieved in March 2016 following submission of the clinical trial application to the Chinese regulatory authority, a $5.0 million milestone payment achieved in June 2023 following NMPA approval of VASCEPA under the MARINE indication, 77 and a $3.0 million milestone payment achieved in October 2023 following a regulatory submission to the NMPA for VASCEPA under the REDUCE-IT indication. • HLS – a $5.0 million upfront payment which was received upon closing of the agreement in September 2017, a $2.5 million milestone payment that was received following achievement of the REDUCE-IT trial primary endpoint in September 2018, a $2.5 million milestone payment that was received following U.S.
As further discussed below, this decrease consists of a $218.0 million decrease in U.S. product revenue, $0.2 million decrease in licensing and royalty revenue, offset by an increase of $4.3 million in net product revenue from sales of VASCEPA outside of the United States. Product revenue, net.
As further discussed below, the aforementioned decrease consists of an $86.0 million decrease in U.S. net product revenue, offset by increases of $18.9 million in licensing and royalty revenue and $4.7 million in net product revenue from sales of VASCEPA outside of the United States. Product revenue, net.
The overall icosapent ethyl market in the United States, based on prescription levels reported by Symphony Health, increased for the year ended December 31, 2022 by 7% as compared to the year ended December 31, 2021.
During the majority of the year ended December 31, 2022 there were three generics in the market. The overall icosapent ethyl market in the United States, based on prescription levels reported by Symphony Health, increased for the year ended December 31, 2023 by 4% as compared to the year ended December 31, 2022.
Restructuring expense consists of restructuring costs incurred under our June 2022 cost reduction plan, the discontinuation of German operations and our September 2021 Go-to-Market strategy implementation, which consists of severance pay, incentive compensation, insurance benefits, stock-based compensation expense and other contract related costs. Interest and other (expense) income, net.
Restructuring expense consists of restructuring costs incurred under our July 2023 ORP, June 2022 Cost Reduction Plan, or CRP, and August 2022 discontinuation of German operations, which consists of severance pay, incentive compensation, insurance benefits, stock-based compensation expense and other contract related costs. Interest income, net and other income (expense), net.
Selling, general and administrative expense for the years ended December 31, 2022 and 2021 was $304.4 million and $408.3 million, respectively, a decrease of $103.9 million, or 25%.
Selling, general and administrative expense for the years ended December 31, 2023 and 2022 was $199.9 million and $304.4 million, respectively, a decrease of $104.5 million, or 34%.
In addition to the United States, we also sell VASCEPA by prescription in certain countries in Europe and is available by prescription in Canada, Lebanon and the United Arab Emirates through collaborations with third-party companies.
In addition to the United States, we also sell VASCEPA by prescription in certain countries in Europe as well as certain countries outside of the United States and Europe, such as China and Canada, through collaborations with third-party companies.
Licensing and royalty revenue during the years ended December 31, 2022 and 2021 was $2.7 million and $2.9 million, respectively, a decrease of 0.2 million, or 6%.
Licensing and royalty revenue during the years ended December 31, 2023 and 2022 was $21.6 million and $2.7 million, respectively, an increase of $18.9 million, or 706%.
In accordance with ASC 205-40, management is required to evaluate our ability to continue as a going concern for at least one year after the date of the financial statements are issued.
As of December 31, 2023, we had cash and cash equivalents of $199.3 million and short-term investments of $121.4 million. In accordance with ASC 205-40, management is required to evaluate our ability to continue as a going concern for at least one year after the date the financial statements are issued.
On April 22, 2021, we announced that we received marketing authorization from the Medicines and Healthcare Products Regulatory Agency, or MHRA, for VAZKEPA in England, Wales and Scotland to reduce cardiovascular risk. VASCEPA is currently available by prescription in the U.S. and certain other countries throughout the world, as described below.
On April 22, 2021, we announced that we received marketing authorization from the Medicines and Healthcare Products Regulatory Agency, or MHRA, for VAZKEPA in England, Wales and Scotland to reduce cardiovascular risk.
Selling, general and administrative expenses for the years ended December 31, 2022 and 2021 are summarized in the table below: Year Ended December 31, In thousands 2022 2021 Selling expense (1) $ 185,614 $ 266,474 General and administrative expenses (2) 96,462 109,555 Non-cash stock-based compensation expense (3) 22,340 32,305 Total selling, general and administrative expense $ 304,416 $ 408,334 (1) Selling expense for the years ended December 31, 2022 and 2021 was $185.6 million and $266.5 million, respectively, a decrease of $80.9 million, or 30%.
Selling, general and administrative expenses for the years ended December 31, 2023 and 2022 are summarized in the table below: Year Ended December 31, In thousands 2023 2022 Selling expense (1) $ 111,326 $ 185,614 General and administrative expenses (2) 76,119 96,462 Non-cash stock-based compensation expense (3) 12,493 22,340 Total selling, general and administrative expense $ 199,938 $ 304,416 (1) Selling expense for the years ended December 31, 2023 and 2022 was $111.3 million and $185.6 million, respectively, a decrease of $74.3 million, or 40%.
We recorded product revenue, net, of $366.5 million and $580.3 million during the years ended December 31, 2022 and 2021, respectively, a decrease of $213.8 million, or 37%. This decrease was driven primarily by a 38% decrease in VASCEPA sales to our customers in the United States.
We recorded product revenue, net, of $285.3 million and $366.5 million during the years ended December 31, 2023 and 2022, respectively, a decrease of $81.2 million, or 22%. This decrease was due primarily to a 24% decrease in VASCEPA sales in the United States.
Other We continue to assess other potential partnership opportunities for VASCEPA with companies outside of the United States and Europe with the intention of partnering in all other international markets where VASCEPA receives local regulatory approval.
We continue to assess other potential partnership opportunities for VASCEPA with companies outside of the United States and Europe with the intention of partnering in all other international markets where VASCEPA receives local regulatory approval. 72 Research and Development Since its inception in 2011, conduct of the REDUCE-IT cardiovascular outcomes study of VASCEPA has been the centerpiece of our research and development.
Privacy laws and other factors impact the availability of data to inform European commercial operations at an individual physician level. Generally, less data is available and at reduced frequencies than in the United States. However, this greater concentration of at-risk patients being treated by specialists in Europe should allow for more efficient promotion than in the United States.
Patients at high-risk for cardiovascular disease tend to be treated more often by specialists, such as cardiologists rather than by general practitioners. Privacy laws and other factors impact the availability of data to inform European commercial operations at an individual physician level. Generally, less data is available and at reduced frequencies than in the United States.
On February 23, 2022 the Hong Kong Department of Health completed their evaluation of the clinical trial conducted in China and approved the use of VASCEPA under the REDUCE-IT indication.
On February 9, 2021, we announced that the regulatory review processes in Mainland China and Hong Kong had commenced. On February 23, 2022, the Hong Kong Department of Health completed their regulatory evaluation and approved the use of VASCEPA under the REDUCE-IT indication.
Research and development expenses for the years ended December 31, 2022 and 2021 are summarized in the table below: Year Ended December 31, In thousands 2022 2021 REDUCE-IT study (1) $ 1,724 $ 3,607 Fixed-dose combination (2) 5,777 — Regulatory filing fees and expenses (3) 1,959 1,441 Internal staffing, overhead and other (4) 16,486 19,932 Research and development expense, excluding non-cash expense 25,946 24,980 Non-cash stock-based compensation expense (5) 4,465 4,327 Total research and development expense $ 30,411 $ 29,307 (1) The decrease in expenses for the REDUCE-IT study is primarily driven by the decrease in the number of analyses performed beyond the original REDUCE-IT cardiovascular outcomes trial.
Research and development expenses for the years ended December 31, 2023 and 2022 are summarized in the table below: Year Ended December 31, In thousands 2023 2022 REDUCE-IT study (1) $ 1,020 $ 1,724 Fixed-dose combination (2) 1,395 5,777 Regulatory filing fees and expenses (3) 966 1,959 Internal staffing, overhead and other (4) 14,651 16,486 Research and development expense, excluding non-cash expense 18,032 25,946 Non-cash stock-based compensation expense (5) 4,187 4,465 Total research and development expense $ 22,219 $ 30,411 (1) The decrease in expenses for the REDUCE-IT study is primarily driven by incremental efficiencies applied to ongoing analyses performed on the REDUCE-IT cardiovascular outcomes trial data, further leveraging existing internal resources compared to outsourced support.
Normalized total prescriptions represent the estimated total number of VASCEPA prescriptions dispensed to patients, calculated on a normalized basis (i.e., one month’s supply, or total capsules dispensed multiplied by the number of grams per capsule divided by 120 grams). Inventory levels at wholesalers tend to fluctuate based on seasonal factors, prescription trends and other factors.
Based on data from Symphony Health, the below chart represents the estimated number of normalized total VASCEPA prescriptions. Normalized total prescriptions represent the estimated total number of VASCEPA prescriptions dispensed to patients, calculated on a normalized basis (i.e., one month’s supply, or total capsules dispensed multiplied by the number of grams per capsule divided by 120 grams).
Our cash flows from operating, investing and financing activities, as reflected in the consolidated statements of cash flows, are summarized in the following table: Year Ended December 31, In millions 2022 2021 2020 Cash (used in) provided by: Operating activities $ (180.1 ) $ (66.5 ) $ (21.7 ) Investing activities 175.3 104.1 (377.0 ) Financing activities (0.4 ) (5.1 ) (58.9 ) Increase (decrease) in cash and cash equivalents and restricted cash $ (5.2 ) $ 32.5 $ (457.6 ) Net cash used in operating activities during 2022 compared to 2021 increased primarily as a result of a decrease in U.S. product revenue, costs associated with commercial and pre-launch operations in Europe as well as an increase in inventory purchases in the first half of 2022.
Our cash flows from operating, investing and financing activities, as reflected in the consolidated statements of cash flows, are summarized in the following table: Year Ended December 31, In millions 2023 2022 2021 Cash provided by (used in): Operating activities $ 6.9 $ (180.1 ) $ (66.5 ) Investing activities (25.5 ) 175.3 104.1 Financing activities 0.2 (0.4 ) (5.1 ) (Decrease) increase in cash and cash equivalents and restricted cash $ (18.4 ) $ (5.2 ) $ 32.5 Net cash provided by operating activities increased during 2023 as compared to net cash used in operating activities during the same period in 2022.
On February 9, 2021, we announced that the regulatory review processes in Mainland China and Hong Kong have commenced. The National Medical Products Administration, or NMPA, accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from our prior studies of VASCEPA.
In Mainland China, the NMPA accepted for review the new drug 71 application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from our prior studies of VASCEPA.
Net cash provided by investing activities during the year ended December 31, 2022 is primarily due to the proceeds from the maturity of $257.5 million in investment-grade interest bearing instruments, partially offset by $81.6 million in purchases of investment-grade interest bearing instruments as compared to the same period in 2021 where proceeds from the maturity of investment-grade interest bearing instruments was $394.3 million, partially offset by $290.2 million in purchases of investment-grade interest bearing instruments.
This is primarily due to the purchase of investment grade interest bearing instruments of $215.1 million partially offset by $190.1 million from proceeds from the maturity of investment grade interest bearing instruments, as compared to the same period in 2022 where proceeds from the maturity of investment grade interest bearing instruments was $257.5 million, partially offset by $81.6 million in purchases of investment grade interest bearing instruments.
Additionally, based on prescription levels reported by Symphony Health, VASCEPA branded prescriptions decreased by 19% in the year ended December 31, 2022 as compared to the year ended December 31, 2021.
Our share of the icosapent ethyl market has decreased to approximately 57% in the year ended December 31, 2023 from approximately 60% in the year ended December 31, 2022. Additionally, based on prescription levels reported by Symphony Health, VASCEPA branded prescriptions decreased by 8% in the year ended December 31, 2023 as compared to the year ended December 31, 2022.
We have written contracts with our distributors, and transfer of control typically occurs upon delivery of our product to the Distributor. We evaluate the creditworthiness of each of our distributors to determine whether revenues can be recognized upon delivery, subject to satisfaction of the other requirements, or whether recognition is required to be delayed until receipt of payment.
We evaluate the creditworthiness of each of our distributors to determine whether revenues can be recognized upon delivery, subject to satisfaction of the other requirements, or whether recognition is required to be delayed until receipt of payment. We calculate gross product revenues based on the wholesale acquisition cost charged to our distributors for VASCEPA.
Research and development expense for the years ended December 31, 2022 and 2021 was $30.4 million and $29.3 million, respectively, an increase of $1.1 million, or 4%.
Research and development expense. Research and development expense for the years ended December 31, 2023 and 2022 was $22.2 million and $30.4 million, respectively, a decrease of $8.2 million, or 27%.
We are implementing an impactful and cost-effective hybrid commercial model balancing optimally digital and face-to-face approach for more impact and cost efficiency, which is or will be utilized throughout Europe as launches are rolled out. Patients at high risk for cardiovascular disease tend to be treated more often by specialists, such as cardiologists rather than by general practitioners.
We are leveraging third-party relationships for various support activities and are implementing an impactful and cost-effective hybrid commercial model balancing optimally digital and face-to-face approach for more impact and cost efficiency, which is or will be utilized throughout Europe as launches are rolled out.
The previous calculations of prescription levels by this vendor can change between periods and can be significantly affected by lags in data reporting from various sources or by changes in pharmacies and other distributors providing data. Such methods can from time to time result in significant inaccuracies in information when ultimately compared with actual results.
Inventory levels at wholesalers tend to fluctuate based on seasonal factors, prescription trends and other factors. The previous calculations of prescription levels by this vendor can change between periods and can be significantly affected by lags in data reporting from various sources or by changes in pharmacies and other distributors providing data.
In Europe, VAZKEPA has the benefit of ten years of market protection, and we have been issued a patent that expires in 2033 with additional pending applications that could extend exclusivity into 2039.
However, this greater concentration of at-risk patients being treated by specialists in Europe should allow for more efficient promotion than in the United States. In Europe, VAZKEPA has the benefit of 10 years of market protection, and we have been issued a patent that expires in 2033 with additional pending applications that could extend exclusivity into 2039.
(3) Non-cash stock-based compensation expense for the years ended December 31, 2022 and 2021 was $22.3 million and $32.3 million, respectively, a decrease of $10.0 million, or 31%. Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to internal personnel supporting our selling, general and administrative functions.
Non-cash stock-based compensation expense represents the estimated costs associated with equity awards issued to internal personnel supporting our selling, general and administrative functions.
To date we have filed thirteen dossiers to gain market access in European countries, including in all of the largest countries in Europe. In most European countries, securing product reimbursement is a requisite to launching. In certain countries, such as Denmark, individual patient reimbursement is allowed prior to national, general organization reimbursement.
Launch of VAZKEPA in individual countries depends on the timing of achieving product reimbursement on a country-by-country basis. To date we have filed 15 dossiers to gain market access in European countries, including in all of the largest countries in Europe. In most European countries, securing product reimbursement is a requisite to launching.
We are not responsible for the accuracy of this vendor's information and we do not receive prescription data directly from retail pharmacies. Europe In 2021, we received marketing authorization and regulatory approval in the EU, England, Wales and Scotland. Launch of VAZKEPA in individual countries depends on the timing of achieving product reimbursement on a country-by-country basis.
Further, data for a single and limited period may not be representative of a trend or otherwise predictive of future results. We are not responsible for the accuracy of this vendor's information and we do not receive prescription data directly from retail pharmacies. Europe In 2021, we received marketing authorization and regulatory approval in the EU, England, Wales and Scotland.
Other (expense) income, net, for the year ended December 31, 2022 and 2021 was expense of $0.7 million and $0.3 million, respectively. Other (expense) income, net, in the years ended December 31, 2022 and 2021 primarily consists of gains and losses on foreign exchange transactions. Provision for income taxes .
Other income (expense), net, primarily consists of the ERC awarded as part of the CARES Act, gains and losses on foreign exchange transactions and sublease income related to our Bridgewater, NJ facility. Provision for income taxes . Provision for income taxes for the year ended December 31, 2023 and 2022 was $5.4 million and $2.0 million, respectively.

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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 changeOur portfolio of held-to-maturity investments as of December 31, 2022 was composed of U.S. Treasury securities, commercial paper, corporate, CD and asset-backed securities and other government-related securities. At December 31, 2022 and 2021, we had short-term investments and long-term investments of $93.0 million and $269.7 million, respectively.
Biggest changeOur portfolio of investments as of December 31, 2023 was composed primarily of U.S. Treasury securities and other government-related securities. At December 31, 2023 and 2022, we had short-term investments and long-term investments of $121.4 million and $93.0 million, respectively.
Additionally, our investment policy is to invest only in institutions that meet high credit quality and diversification standards and established limits on the amount and time to maturity of investments. Item 8. Financial Statement s and Supplementary Data Our consolidated financial statements are annexed to this Annual Report on Form 10-K beginning on page F-1. Item 9.
Additionally, our investment policy is to invest only in institutions that meet high credit quality and diversification standards and established limits on the amount and time to maturity of investments. 81 Item 8. Financial Statement s and Supplementary Data Our consolidated financial statements are annexed to this Annual Report on Form 10-K beginning on page F-1. Item 9.
We believe that we are not exposed to significant interest rate risk through market value fluctuations of balance sheet items (i.e., price risk) or through changes in interest income or expenses (i.e., re-financing or re-investment risk). Interest rate risk mainly arises through interest bearing liabilities and assets.
We believe that we are not exposed to significant interest rate risk through market value fluctuations of balance sheet items (i.e., price risk) or through changes in interest income or expenses (i.e., refinancing or reinvestment risk). Interest rate risk mainly arises through interest bearing liabilities and assets.
We monitor our investments with our investment managers with the objective of minimizing concentrations of credit risks. Our short-term investments consist of held-to-maturity securities that will be due in one year or less. Our long-term investments consist of held-to-maturity securities that will be due in more than one year.
We monitor our investments with our investment managers with the objective of minimizing concentrations of credit risks. Our short-term investments consist of securities that mature in one year or less. Our long-term investments consist of securities that mature in more than one year.

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