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What changed in AMICUS THERAPEUTICS, INC.'s 10-K — 2023 vs 2024

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

+358 added−383 removedSource: 10-K (2025-02-19) vs 10-K (2024-02-28)

Top changes in AMICUS THERAPEUTICS, INC.'s 2024 10-K

358 paragraphs added · 383 removed · 309 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

62 edited+7 added−25 removed200 unchanged
Biggest changeThus approval of a 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of an NCE, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph 4 certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant. -17- Table of Contents Biologics Price Competition and Innovation Act The Biologics Price Competition and Innovation Act of 2009 ("BPCIA"), which was enacted as part of the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 ("PPACA") created an abbreviated approval pathway for biological products that are demonstrated to be "biosimilar" or "interchangeable" with an FDA-licensed reference biological product via an approved BLA.
Biggest changeThus approval of a 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of an NCE, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph 4 certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. civil False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, 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 and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S. federal government; • U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; -18- Table of Contents • state laws and regulations, including state anti-kickback and false claims laws, that may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payer, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and • the Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to CMS information related to certain payments made in the preceding calendar year and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; beginning in 2022, applicable manufacturers are required to report such information regarding payments and transfers of value provided, as well as ownership and investment interests held, during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. civil False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, 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 and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S. federal government; -18- Table of Contents • U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • state laws and regulations, including state anti-kickback and false claims laws, that may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payer, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and • the Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to CMS information related to certain payments made in the preceding calendar year and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; beginning in 2022, applicable manufacturers are required to report such information regarding payments and transfers of value provided, as well as ownership and investment interests held, during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives.
Priority Review Under FDA policies, a drug candidate is eligible for priority review, or review within six months from filing for a new molecular entity ("NME") or six months from submission for a non-NME if the drug candidate provides a significant improvement compared to marketed drugs in the treatment, diagnosis, or prevention of a disease, rather than the standard review of ten months under current PDUFA guidelines.
Priority Review Under FDA policies, a drug candidate is eligible for priority review, or review within six months from filing for a new molecular entity ("NME") or six months from submission for a non-NME if the drug candidate provides a significant improvement compared to marketed drugs in the treatment, diagnosis, or prevention of a disease, rather than the standard review of ten months under current PDUFA V guidelines.
Miglustat is not an active ingredient that contributes directly to glycogen reduction. In addition, clinical studies are ongoing in pediatric patients for both the late-onset Pompe disease ("LOPD") and infantile-onset Pompe disease ("IOPD") populations. Next-Generation for Pompe Disease We are committed to continued innovation for all people living with Pompe disease.
Miglustat is not an active ingredient that contributes directly to glycogen reduction. In addition, clinical studies are ongoing in pediatric patients for both the LOPD and infantile-onset Pompe disease ("IOPD") populations. Next-Generation for Pompe Disease We are committed to continued innovation for all people living with Pompe disease.
Galafold ® was approved in the E.U. and U.K. in May 2016 as a first-line therapy for long-term treatment of adults and adolescents, aged 16 years and older, with a confirmed diagnosis of Fabry disease and who have an amenable mutation (variant).
Galafold ® was approved in the E.U. and U.K. in May 2016 as a first-line therapy for long-term treatment of adults and adolescents, aged 16 years and older, with a confirmed diagnosis of Fabry disease and who have an amenable variant.
We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. Highlights of our progress include: • Commercial and regulatory success in Fabry disease .
We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. Highlights of our progress include: • Commercial success in Fabry disease .
For example, we own or hold license rights to U.S. and foreign patents or patent applications covering the following: • Next-generation Fabry chaperones; • Gene therapy protein engineering technology; • Gene therapy (e.g., Pompe, Fabry) and ERT (e.g., CDKL5) programs and their use to treat specified diseases.
For example, we own or hold license rights to U.S. and foreign patents or patent applications covering the following: • Next-generation Fabry chaperones; • Gene therapy protein engineering technology; • Gene therapy (e.g., Pompe, Fabry) programs and their use to treat specified diseases.
Under the terms of the Collaboration Agreement, GSK is eligible to receive post-approval and sales-based milestones up to $40 million, as well as tiered royalties in the mid-teens in eight major markets outside the U.S. Manufacturing We continue to rely on contract manufacturers to supply the active biopharmaceutical ingredients and finished goods for our products and product candidates.
Under the terms of the Collaboration Agreement, GSK is eligible to receive post-approval and sales-based milestones up to $40 million, as well as tiered royalties in the mid-teens in eight major markets outside the U.S. -10- Table of Contents Manufacturing We continue to rely on contract manufacturers to supply the active biopharmaceutical ingredients and finished goods for our products and product candidates.
We cannot be certain, however, that issued patents will be enforceable or provide adequate protection or that pending patent applications will result in issued patents. -8- Table of Contents • Individual patents extend for varying periods depending on the effective date of filing of the patent application or the date of patent issuance, and the legal term of the patents in the countries in which they are obtained.
We cannot be certain, however, that issued patents will be enforceable or provide adequate protection or that pending patent applications will result in issued patents. • Individual patents extend for varying periods depending on the effective date of filing of the patent application or the date of patent issuance, and the legal term of the patents in the countries in which they are obtained.
Under federal law, the submission of most NDAs and BLAs is additionally subject to a substantial application user fee; although for orphan drugs these fees are waived, and the holder of an approved NDA or BLA may also be subject to annual product and establishment user fees.
Under federal law, the submission of most NDAs and BLAs is additionally subject to a substantial application user fee; although for orphan drugs these fees are waived, and the holder of an approved NDA or BLA may also be subject to annual product and establishment user fees. These fees are typically increased annually.
New efficacy claims require submission and approval of an NDA supplement and BLA supplement for each new indication. The efficacy claims typically require new clinical data similar to those included in the original application. The FDA uses the same procedures and actions in reviewing NDA and BLA supplements as it does in reviewing NDAs and BLAs.
New efficacy claims require submission and approval of an NDA supplement and BLA supplement for each new indication. -15- Table of Contents The efficacy claims typically require new clinical data similar to those included in the original application. The FDA uses the same procedures and actions in reviewing NDA and BLA supplements as it does in reviewing NDAs and BLAs.
Patent term extensions and adjustments, supplementary protection certificates, and pediatric exclusivity periods are not reflected in the expiration dates listed above and may extend protection. In addition to our clinical programs, we actively monitor and file patent applications in the U.S. and in foreign countries on relevant technologies and pre-clinical programs.
Patent term extensions and adjustments, supplementary protection certificates, and pediatric exclusivity periods are not reflected in the expiration dates listed above and may extend protection. -8- Table of Contents In addition to our clinical programs, we actively monitor and file patent applications in the U.S. and in foreign countries on relevant technologies and pre-clinical programs.
Any waivers or material amendments to the Code will be posted promptly on our website. -25- Table of Contents
Any waivers or material amendments to the Code will be posted promptly on our website. -24- Table of Contents
Most such applications for standard review are reviewed within 12 months under PDUFA V (two months for filing plus ten months for review). The FDA attempts to review a drug candidate that is eligible for priority review within six months, as discussed below.
Most such applications for standard review are reviewed within 12 months under the Prescription Drug User Fee Act ("PDUFA V") (two months for filing plus ten months for review). The FDA attempts to review a drug candidate that is eligible for priority review within six months, as discussed below.
Additionally, Pombiliti ™ + Opfolda ™ has been granted orphan drug designation in the U.S., E.U., U.K., Japan and several other countries. Our Strategy Our strategy is to create, manufacture, test, and deliver the highest quality medicines for people living with rare diseases through internally developed, jointly developed, acquired, or in-licensed products and product candidates.
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U. Our Strategy Our strategy is to create, manufacture, test, and deliver the highest quality medicines for people living with rare diseases through internally developed, jointly developed, acquired, or in-licensed products and product candidates.
We have obtained an orphan medicinal product designation in the E.U. from the EMA for Galafold ® for the treatment of Fabry disease and the combination product, ATB200/AT2221, for the treatment of Pompe disease.
We have obtained an orphan medicinal product designation in the E.U. from the EMA for Galafold ® for the treatment of Fabry disease and the combination product, Pombiliti ® + Opfolda ® , for the treatment of Pompe disease.
Pombiliti ™ + Opfolda ™ consists of a uniquely engineered rhGAA enzyme, cipaglucosidase alfa-atga, with an optimized carbohydrate structure to enhance lysosomal uptake, administered in combination with miglustat that functions as an enzyme stabilizer. Miglustat binds to and stabilizes cipaglucosidase alfa-atga reducing inactivation of rhGAA in circulation to improve the uptake of active enzyme into key disease relevant tissues.
Pombiliti ® + Opfolda ® consists of a uniquely engineered rhGAA enzyme, cipaglucosidase alfa-atga, with an optimized carbohydrate structure to enhance cellular uptake, administered intravenously in combination with orally administered miglustat. Miglustat binds to and stabilizes the cipaglucosidase alfa-atga in circulation reducing inactivation of rhGAA in circulation to improve the uptake of active enzyme into key disease relevant tissues.
Long-term preclinical safety evaluations, such as animal tests of reproductive toxicity and carcinogenicity, continue during the IND phase of development. Reproductive toxicity studies are required to allow inclusion of women of childbearing potential in clinical trials, whereas carcinogenicity studies are required for registration.
Long-term preclinical safety evaluations, such as animal tests of reproductive toxicity and carcinogenicity, continue during the IND phase of development. Reproductive toxicity studies are required to allow inclusion of women of childbearing potential in clinical trials, whereas carcinogenicity studies are required for registration. The results of these long-term studies would eventually be described in product labeling.
As part of our commitment to our employees, these trainings cover our zero-tolerance policy -24- Table of Contents towards the use of child labor, forced labor, or other forms of modern slavery, educating our workforce on discrimination and harassment, and periodically refreshing the organization’s understanding of our global anti-bribery and corruption policy.
As part of our commitment to our employees, these trainings cover our zero-tolerance policy towards the use of child labor, forced labor, or other forms of modern slavery, and periodically refreshing the organization’s understanding of our global anti-bribery and corruption policy.
GlaxoSmithKline In July 2012, as amended in November 2013, we entered into an agreement with GlaxoSmithKline ("GSK"), pursuant to which Amicus obtained global rights to develop and commercialize Galafold ® as a monotherapy and in combination with ERT for Fabry disease (“Collaboration Agreement”).
The following summarizes our material rights and obligations under those licenses: GlaxoSmithKline In July 2012, as amended in November 2013, we entered into an agreement with GlaxoSmithKline ("GSK"), pursuant to which Amicus obtained global rights to develop and commercialize Galafold ® as a monotherapy and in combination with ERT for Fabry disease (“Collaboration Agreement”).
Orphan drug designation must be requested before submitting an NDA or BLA. After the FDA grants orphan drug designation, the generic identity of the drug and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
After the FDA grants orphan drug designation, the generic identity of the drug and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
The following table lists our principal competitors and publicly available information on the status of their clinical-stage product offerings: -11- Table of Contents Competitor (1) Indication Product Class of Product Status 2023 Sales (in millions) Sanofi Fabry Disease Fabrazyme ® ERT Marketed €991 Pompe Disease Myozyme ® / Lumizyme ® ERT Marketed €783 Pompe Disease Nexviazyme ® / Nexviadyme ® ERT Marketed €425 Fabry Disease Venglustat Oral glucosylceramide synthase ("GCS") Inhibitor Phase 3 N/A Takeda (2) Fabry Disease Replagal ® ERT Marketed ¥71,300 Chiesi (3) Fabry Disease ELFABRIO ® ERT Marketed $14.7 Idorsia Fabry Disease Lucerastat Oral GCS Inhibitor Phase 3 N/A AceLink Fabry Disease AL1211 Oral GCS Inhibitor Phase 1/2 N/A Sangamo Fabry Disease Isaralgagene civaparvovec Gene Therapy Phase 1/2 N/A 4DMT Fabry Disease 4D-310 Gene Therapy Phase 1/2 N/A Bayer Pompe Disease ACTUS-101 Gene Therapy Phase 1/2 N/A Astellas Pompe Disease AT845 Gene Therapy Phase 1/2 N/A Roche Pompe Disease SPK-3006 Gene Therapy Phase 1/2 N/A Maze Pompe Disease MZE001 Oral glycogen synthase ("GYS1") Inhibitor Phase 1/2 N/A _____________________________ (1) Reflects commercial products and product candidates for which IND has been filed or are in clinical development.
The following table lists our principal competitors and publicly available information on the status of their clinical-stage product offerings: -11- Table of Contents Competitor (1) Indication Product Class of Product Status 2024 Sales (in millions) Sanofi Fabry Disease Fabrazyme ® ERT Marketed €1,047 Pompe Disease Myozyme ® / Lumizyme ® ERT Marketed €671 Pompe Disease Nexviazyme ® / Nexviadyme ® ERT Marketed €667 Fabry Disease Venglustat Oral glucosylceramide synthase ("GCS") Inhibitor Phase 3 N/A Takeda (2) Fabry Disease Replagal ® ERT Marketed ¥78,700 Chiesi (3) Fabry Disease ELFABRIO ® ERT Marketed $14.0 Eleva Fabry Disease RPV-001 ERT Phase 1/2 N/A Idorsia Fabry Disease Lucerastat Oral GCS Inhibitor Phase 3 N/A AceLink Fabry Disease AL1211 Oral GCS Inhibitor Phase 1/2 N/A Sangamo Fabry Disease Isaralgagene civaparvovec Gene Therapy Phase 1/2 N/A UniQure Fabry Disease AMT-191 Gene Therapy Phase 1/2 N/A 4DMT Fabry Disease 4D-310 Gene Therapy Phase 1/2 N/A Bayer Pompe Disease ACTUS-101 Gene Therapy Phase 1/2 N/A Astellas Pompe Disease AT845 Gene Therapy Phase 1/2 N/A Roche Pompe Disease SPK-3006 Gene Therapy Phase 1/2 N/A GeneCradle Pompe Disease GC301 Gene Therapy Phase 1/2 N/A Aro Pompe Disease ABX1100 Gene Therapy Phase 1/2 N/A Maze Pompe Disease MZE001 Oral glycogen synthase ("GYS1") Inhibitor Phase 1/2 N/A _____________________________ (1) Reflects commercial products and product candidates for which IND has been filed or are in clinical development.
Pombiliti ™ + Opfolda ™ (also referred to as "cipaglucosidase alfa-atga/miglustat") was approved in 2023 in the three largest Pompe markets: the U.S., the E.U., and the U.K. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., and Switzerland. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Once the submission is accepted for filing, the FDA begins an in-depth review. The FDA has agreed to certain performance goals in the review of NDAs and BLAs. Marketing applications are assigned review status during the filing period. Review status could be either standard or priority.
The FDA has agreed to certain performance goals in the review of NDAs and BLAs. Marketing applications are assigned review status during the filing period. Review status could be either standard or priority.
(2) Reflects running 12 month revenue as of December 31, 2023, as Takeda's fiscal year ends on March 31, 2024. (3) Reflects sales through September 30, 2023. Government Regulation FDA Approval Process In the U.S., biopharmaceutical products, including gene therapies, are subject to extensive regulation by the FDA.
(2) Reflects revenue for the twelve-month period ended December 31, 2024, as Takeda's fiscal year ends on March 31, 2025. (3) Reflects revenue for the twelve-month period ended September 30, 2024. Government Regulation FDA Approval Process In the U.S., biopharmaceutical products, including gene therapies, are subject to extensive regulation by the FDA.
Supporting our global employees and valuing their differences is an essential part of the core values and culture at Amicus. Tied to these values and culture, we believe our success and our ability to help patients depends on our capability to attract, develop and retain key personnel.
Supporting our global employees is an essential part of the core values and culture at Amicus. Tied to these values and culture, we believe our success and our ability to help patients depends on our capability to attract, develop and retain key personnel. As of December 31, 2024, we had 499 full-time employees.
Our Commercial Products and Product Candidates Galafold ® (migalastat HCl) for Fabry Disease Our oral precision medicine Galafold ® was granted accelerated approval by the FDA in August 2018 for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene ("GLA") variant based on in vitro assay data.
Total cash, cash equivalents, and marketable securities as of December 31, 2024 was $249.9 million. -5- Table of Contents Our Commercial Products and Product Candidates Galafold ® (migalastat HCl) for Fabry Disease Our oral precision medicine Galafold ® was granted accelerated approval by the FDA in August 2018 for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene ("GLA") variant based on in vitro assay data.
Marketing authorization approvals as well as approvals for adolescents aged 12 years and older weighing 45 kg or more have been granted in over 40 countries around the world.
Marketing authorization approvals as well as approvals for adolescents aged 12 years and older weighing 45 kg or more have been granted in over 40 countries around the world. We plan to continue to launch Galafold ® in additional countries, upon receipt of marketing authorization.
Our two marketed therapies are Galafold ® , the first oral monotherapy for people living with Fabry disease who have amenable genetic variants, and Pombiliti ™ + Opfolda ™ , a novel treatment designed to improve uptake of active enzyme into key disease relevant tissues for adults living with late-onset Pompe disease.
Our two marketed therapies are Galafold ® , the first oral monotherapy for people living with Fabry disease who have amenable genetic variants, and Pombiliti ® + Opfolda ® , a novel two-component treatment for adults living with late-onset Pompe disease.
These fees are typically increased annually. -13- Table of Contents The FDA has 60 days from its receipt of an NDA or BLA to determine whether the application will be accepted for filing based on the agency's threshold determination that it is sufficiently complete to permit substantive review.
The FDA has 60 days from its receipt of an NDA or BLA to determine whether the application will be accepted for filing based on the agency's threshold determination that it is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-depth review.
For the year ended December 31, 2023 Pombiliti ™ + Opfolda ™ revenue was $11.6 million of consolidated revenue. Pombiliti ™ + Opfolda ™ were approved by the European Commission ("EC") in June 2023, the Medicines and Healthcare products Regulatory Agency ("MHRA)" of the United Kingdom in August 2023, and the U.S.
For the year ended December 31, 2024, Pombiliti ® + Opfolda ® revenue was $70.2 million of consolidated revenue. Pombiliti ® + Opfolda ® were approved by the European Commission ("EC"), the Medicines and Healthcare products Regulatory Agency ("MHRA)" of the United Kingdom, and the U.S. Food and Drug Administration ("FDA") in 2023 and the Swissmedic of Switzerland in 2024.
This approval mechanism is provided for under 21CRF314 Subpart H and Subpart E. In this case, clinical trials are conducted in which a surrogate endpoint is used as the primary outcome for approval.
In this case, clinical trials are conducted in which a surrogate endpoint is used as the primary outcome for approval.
Breakthrough Therapy Designation Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Additionally, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process. -16- Table of Contents Breakthrough Therapy Designation Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
For the year ended December 31, 2023, Galafold ® revenue was $387.8 million of consolidated revenue, which represented an increase of $58.7 million compared to the prior year. We continue to see strong commercial momentum and expansion into additional geographies. • Pompe disease program milestones .
For the year ended December 31, 2024, Galafold ® revenue was $458.1 million of consolidated revenue, which represented an increase of $70.3 million compared to the prior year. We continue to see strong commercial momentum and expansion into additional geographies. • Commercial and regulatory success in Pompe disease .
These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, as well as in acquiring technologies complementary to, or necessary for, our programs.
These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, as well as in acquiring technologies complementary to, or necessary for, our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
Our Corporate Information We were incorporated under the laws of the State of Delaware on February 4, 2002. The address of our global headquarters is 47 Hulfish Street, Princeton, NJ 08542 and our telephone number is 609-662-2000. Our website address is www.amicusrx.com .
The address of our global headquarters is 47 Hulfish Street, Princeton, NJ 08542 and our telephone number is 609-662-2000. Our website address is www.amicusrx.com .
The FDA has established the Office of Tissue and Advanced Therapies within the Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER in its review.
The FDA has established the Office of Tissue and Advanced Therapies within the Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER in its review. -13- Table of Contents In addition to the regulations discussed above, there are a number of additional standards that apply to clinical trials involving gene therapies.
A certification that the new product will not infringe the already approved product's listed patents or that such patents are invalid is called a Paragraph 4 certification.
A certification that the new product will not infringe the already approved product's listed patents or that such patents are invalid is called a Paragraph 4 certification. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired.
We have certain obligations under these acquisitions or licensing agreements, including diligence obligations and payments, which are contingent upon achieving various development, regulatory and commercial milestones.
Collaboration and License Agreements We have acquired rights to develop and commercialize our product candidates through licenses granted by various parties. We have certain obligations under these acquisitions or licensing agreements, including diligence obligations and payments, which are contingent upon achieving various development, regulatory and commercial milestones.
Pombiliti ™ + Opfolda ™ were approved by the EC in June 2023, the MHRA in August 2023, and the FDA in September 2023. Additional regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® was approved by the EC, the MHRA and the FDA in 2023, and the Swissmedic in 2024 for adult late-onset Pompe disease ("LOPD") patients. Additional regulatory submissions and reimbursement processes with global health authorities are currently underway.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. -10- Table of Contents Our commercial opportunities could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer side effects, are more convenient, and/or are less expensive than products that we may develop.
Our commercial opportunities could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer side effects, are more convenient, and/or are less expensive than products that we may develop.
Fabry Disease Background Patients with Fabry disease have an inherited deficiency of the alpha-Gal A enzyme that would normally degrade the lipid substrate globotriaosylceramide in the lysosome.
As part of our long-term commitment, we are also continuing discovery for next-generation genetic medicines. Fabry Disease Background Patients with Fabry disease have an inherited deficiency of the alpha-Gal A enzyme that would normally degrade the lipid substrate globotriaosylceramide in the lysosome.
To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already-approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent as an ANDA applicant.
The FDA may then approve the new product candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant. -17- Table of Contents To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already-approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent as an ANDA applicant.
If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. -14- Table of Contents If the ANDA applicant submits a Paragraph 4 certification to the FDA, the applicant must also send notice of the Paragraph 4 certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA.
If the ANDA applicant submits a Paragraph 4 certification to the FDA, the applicant must also send notice of the Paragraph 4 certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA.
We plan to continue to launch Galafold ® in additional countries, including for adolescents aged 12 years and older. -5- Table of Contents As an orally administered monotherapy, Galafold ® is designed to bind to and stabilize an endogenous alpha-galactosidase A ("alpha-Gal A") enzyme in those patients with genetic variants identified as amenable in a Good Laboratory Practice ("GLP") cell-based amenability assay.
As an orally administered monotherapy, Galafold ® is designed to bind to and stabilize an endogenous alpha-galactosidase A ("alpha-Gal A") enzyme in those patients with genetic variants identified as amenable in a Good Laboratory Practice ("GLP") cell-based amenability assay. Next-Generation for Fabry Disease We are committed to continued innovation for all people living with Fabry disease.
The Hatch-Waxman Act In seeking approval for a drug through an NDA, applicants are required to list with the FDA certain patent(s) with claims that cover the applicant's product or approved method of use.
Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained, problems are identified following initial marketing, or post-marketing commitments are not met. -14- Table of Contents The Hatch-Waxman Act In seeking approval for a drug through an NDA, applicants are required to list with the FDA certain patent(s) with claims that cover the applicant's product or approved method of use.
Strategic Alliances and Arrangements We will continue to evaluate business development opportunities as appropriate to build stockholder value and provide us with access to the financial, technical, clinical, and commercial resources and intellectual property necessary to develop and market technologies or products with a focus on rare and orphan diseases.
Currently, two products, both ERTs, are approved for the treatment of Pompe disease: alglucosidase alfa and avalglucosidase alfa-ngpt by Sanofi Aventis. -7- Table of Contents Strategic Alliances and Arrangements We will continue to evaluate business development opportunities to build stockholder value and provide us with access to the financial, technical, clinical, commercial resources, and intellectual property necessary to develop and market technologies or products in rare and orphan diseases.
Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to file a marketing application, to issue complete response letters or to not approve pending NDAs or BLAs, or to issue warning letters, untitled letters, Form 483s, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, litigation, government investigation, and criminal prosecution.
Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to file a marketing application, to issue complete response letters or to not approve pending NDAs or Biologics License Applications ("BLAs"), or to issue warning letters, untitled letters, Form 483s, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, litigation, government investigation, and criminal prosecution. -12- Table of Contents Biopharmaceutical product development in the U.S. typically involves nonclinical laboratory and animal tests, the submission to the FDA of an Investigational New Drug application ("IND"), which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought.
As such, the scheduled Markman hearing was deemed unneeded and cancelled. The patent positions of companies like ours are generally uncertain and involve complex legal, technical, scientific, and factual questions.
Department of Justice. -9- Table of Contents The patent positions of companies like ours are generally uncertain and involve complex legal, technical, scientific, and factual questions.
The FDA makes its determination of priority or standard review during the 60-day filing period after an initial NDA or BLA submission. -16- Table of Contents Accelerated Approval Under the FDA's accelerated approval regulations, the FDA may approve a drug for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit.
Accelerated Approval Under the FDA's accelerated approval regulations, the FDA may approve a drug for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit. This approval mechanism is provided for under 21CRF314 Subpart H and Subpart E.
Additionally, we strive to attract and retain the most talented employees in the industry and across the globe by offering competitive compensation and benefits that support their health, financial and emotional well-being. Our compensation philosophy is based on rewarding each employee’s individual contributions and striving to achieve equal pay for equal work regardless of gender, race or ethnicity.
Additionally, we strive to attract and retain the most talented employees in the industry and across -23- Table of Contents the globe by offering competitive compensation and benefits that support their health, financial and emotional well-being.
Currently, three other products, all ERTs, are approved for the treatment of Fabry disease: agalsidase beta by Sanofi Aventis, pegunigalsidase alfa-iwxj by Chiesi Farmaceutici and agalsidase alfa by Takeda, the last of which is not approved in the U.S. -6- Table of Contents Pombiliti ™ (cipaglucosidase alfa-atga) + Opfolda ™ (miglustat) for Pompe Disease We have leveraged our biologics capabilities to develop Pombiliti ™ + Opfolda ™ , a novel treatment paradigm for late-onset Pompe disease.
A number of factors are contributing to the continued expansion of Fabry diagnosis, including newborn screening in several states in the U.S., family screening, and access to lower cost genetic testing. -6- Table of Contents Currently, three other products, all ERTs, are approved for the treatment of Fabry disease: agalsidase beta by Sanofi Aventis, pegunigalsidase alfa-iwxj by Chiesi Farmaceutici and agalsidase alfa by Takeda, the last of which is not approved in the U.S.
The IND becomes effective 30 days after its receipt by the FDA, and trials may begin at that point unless the FDA notifies the sponsor that the investigations are subject to a clinical hold. Clinical trials usually involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator.
A 30-day review period after the submission and receipt of an IND is required prior to the commencement of clinical testing in humans. The IND becomes effective 30 days after its receipt by the FDA, and trials may begin at that point unless the FDA notifies the sponsor that the investigations are subject to a clinical hold.
To the extent that our consultants, contractors, or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. -9- Table of Contents Collaboration and License Agreements We have acquired rights to develop and commercialize our product candidates through licenses granted by various parties.
In addition, our trade secrets may otherwise become known or be discovered independently by others. To the extent that our consultants, contractors, or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.
Our Mission to ‘Always Put Patients First’ helps keep our employees engaged with this sense of purpose.
As of December 31, 2024, 58% of our global workforce, 42% of our executive management team and 33% of our Board of Directors were women. Our Mission to ‘Always Put Patients First’ helps keep our employees engaged with this sense of purpose.
These opportunities may include business combinations, partnerships, the strategic out-licensing of certain assets, or the acquisition of preclinical-stage, clinical-stage, or marketed products or platform technologies consistent with our strategic plan to develop and provide therapies to patients living with rare and orphan diseases. -7- Table of Contents Intellectual Property Patents and Trade Secrets Our success depends in part on our ability to maintain proprietary protection surrounding our product candidates, technology, and know-how, to operate without infringing the proprietary rights of others, and to prevent others from infringing our proprietary rights.
Intellectual Property Patents and Trade Secrets Our success depends in part on our ability to maintain proprietary protection surrounding our product candidates, technology, and know-how, to operate without infringing the proprietary rights of others, and to prevent others from infringing our proprietary rights.
Food and Drug Administration ("FDA") in September 2023. • Pipeline advancement and growth. We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. • Financial strength. Total cash, cash equivalents, and marketable securities as of December 31, 2023 was $286.2 million.
Additionally, in 2024, we established reimbursement agreements in multiple E.U. countries, including Spain, Czechia, Italy, Switzerland, and Sweden. • Pipeline advancement and growth. We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. • Financial strength.
Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered. -15- Table of Contents Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the U.S.
Orphan Drugs Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the U.S. Orphan drug designation must be requested before submitting an NDA or BLA.
A Fast Track designated drug candidate would ordinarily meet the FDA's criteria for priority review.
A Fast Track designated drug candidate would ordinarily meet the FDA's criteria for priority review. The FDA makes its determination of priority or standard review during the 60-day filing period after an initial NDA or BLA submission.
Accordingly, manufacturers must continue to expend time, money, and effort in the areas of production and quality control to maintain compliance with cGMP.
Accordingly, manufacturers must continue to expend time, money, and effort in the areas of production and quality control to maintain compliance with cGMP. Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.
The FDA may also require companies to perform additional studies or measurements to support the change from the approved product. The FDA may then approve the new product candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.
The FDA may also require companies to perform additional studies or measurements to support the change from the approved product.
There have been significant ongoing judicial, administrative, executive and legislative efforts to modify or eliminate the Affordable Care Act. For example, the Tax Act enacted on December 22, 2017, repealed the shared responsibility payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code, commonly referred to as the individual mandate.
There have been significant ongoing judicial, administrative, executive and legislative efforts to modify or eliminate the Affordable Care Act.
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Next-Generation for Fabry Disease We are committed to continued innovation for all people living with Fabry disease. As part of our long-term commitment, we are also continuing discovery for next-generation genetic medicines and have an academic research collaboration agreement to explore next-generation pharmacological chaperones for Fabry disease.
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Pombiliti ® (cipaglucosidase alfa-atga) + Opfolda ® (miglustat) for Pompe Disease We have leveraged our biologics capabilities to develop Pombiliti ® + Opfolda ® , a novel two-component treatment paradigm for Pompe disease.
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Currently, two products, both ERTs, are approved for the treatment of Pompe disease: alglucosidase alfa and avalglucosidase alfa-ngpt by Sanofi Aventis.
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We are exploring potential collaborations, alliances, and various other business development opportunities on a regular basis. These opportunities may include business combinations, partnerships, the strategic out-licensing of certain assets, or the acquisition of preclinical-stage, clinical-stage, or marketed products or novel technologies consistent with our corporate strategy to develop and provide therapies to patients living with rare and orphan diseases.
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We are exploring potential collaborations, alliances, and various other business development opportunities on a regular basis.
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As such, the scheduled Markman hearing was deemed unneeded and cancelled. In October 2024, the Company entered into a non-exclusive, non-transferable, royalty-free, fully paid-up license with Teva which will allow Teva to market its generic version of Galafold ® in the United States beginning on January 30, 2037, or earlier in certain circumstances.
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However, in the U.S. we will not know what, if any, extensions are available until a drug is approved.
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In accordance with the license agreement, a consent judgment and permanent injunction was entered with the Court and all Hatch-Waxman litigation between Amicus and Teva has been terminated. As required by law, Amicus and Teva have submitted the confidential license agreement to the U.S. Federal Trade Commission and the U.S.
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In addition, our trade secrets may otherwise become known or be discovered independently by others.
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Clinical trials usually involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator.
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The following summarizes our material rights and obligations under those licenses: University of Pennsylvania In December 2022, we entered into a license agreement with Penn pursuant to which we obtained a license with respect to the pre-clinical research and development of next-generation parvovirus gene therapy products for the treatment of Pompe disease and Fabry disease.
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Biologics Price Competition and Innovation Act The Biologics Price Competition and Innovation Act of 2009 ("BPCIA"), which was enacted as part of the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 ("PPACA") created an abbreviated approval pathway for biological products that are demonstrated to be "biosimilar" or "interchangeable" with an FDA-licensed reference biological product via an approved BLA.
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Under the agreement, we will be responsible for clinical development and commercialization of the licensed products for the indications and Penn is eligible to receive certain milestone and royalty payments with respect to licensed products for each indication, up to an aggregate of $86.5 million per indication.
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Our compensation philosophy is based on rewarding each employee’s individual contributions and striving to achieve equal pay for equal work regardless of gender, race or ethnicity. Our Corporate Information We were incorporated under the laws of the State of Delaware on February 4, 2002.
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Royalty payments are based on net sales of licensed products on a licensed product-by-licensed product and country-by-country basis.
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Biopharmaceutical product development in the U.S. typically involves nonclinical laboratory and animal tests, the submission to the FDA of an Investigational New Drug application ("IND"), which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought.
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The results of these long-term studies would eventually be described in product labeling. -12- Table of Contents A 30-day review period after the submission and receipt of an IND is required prior to the commencement of clinical testing in humans.
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In addition to the regulations discussed above, there are a number of additional standards that apply to clinical trials involving gene therapies.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

196 edited+38 added−42 removed324 unchanged
Biggest changeAmong others, these provisions: • establish a classified board of directors, and, as a result, not all directors are elected at one time; • allow the authorized number of our directors to be changed only by resolution of our board of directors; • limit the manner in which stockholders can remove directors from our board of directors; • establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors; • require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent; • limit who may call stockholder meetings; • authorize our board of directors to issue preferred stock, without stockholder approval, which could be used to institute a "poison pill" that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and • require the approval of the holders of at least 67% of the outstanding voting stock to amend or repeal certain provisions of our charter or bylaws. -63- Table of Contents Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.
Biggest changeAmong others, these provisions: • establish a classified board of directors, and, as a result, not all directors are elected at one time; • allow the authorized number of our directors to be changed only by resolution of our board of directors; • limit the manner in which stockholders can remove directors from our board of directors; • establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors; • require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent; • limit who may call stockholder meetings; • authorize our board of directors to issue preferred stock, without stockholder approval, which could be used to institute a "poison pill" that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and • require the approval of the holders of at least 67% of the outstanding voting stock to amend or repeal certain provisions of our charter or bylaws.
As of 2022, Galafold ® also faces potential generic competition, with Hatch-Waxman litigation currently on-going. In addition, Sanofi markets and sells Myozyme ® , Lumizyme ® , Nexviazyme ® , and Nexviadyme ® for the treatment of Pompe disease.
As of 2022, Galafold ® also faces potential generic competition, with Hatch-Waxman litigation currently on-going. In addition, Sanofi markets and sells Myozyme ® , Lumizyme ® , Nexviazyme ® , Nexviadyme ® for the treatment of Pompe disease.
In addition, if we obtain regulatory approvals for our product candidates, manufacturing efficiency and marketing capabilities are likely to be significant competitive factors. We currently rely on third-party manufacturers for our products and all of our product candidates.
In addition, if we obtain regulatory approvals for our product candidates, manufacturing efficiency and marketing capabilities are likely to be significant competitive factors. We currently rely on third-party manufacturers for all of our products and product candidates.
Department of Health and Human Services that would require manufacturers to charge a negotiated "maximum fair price" for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and requires manufacturers to provide discounts on Part D drugs.
Department of Health and Human Services that would require manufacturers to charge a negotiated "maximum fair price" for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and requires manufacturers to provide discounts on Medicare Part D drugs.
Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any products that we may develop.
The Federal Food, Drug, and Cosmetic Act, or the FD&C Act, FDA regulations and other applicable regulations and policies provide incentives to manufacturers to create modified, non-infringing versions of a drug to facilitate the approval of an ANDA or other application for generic substitutes.
The Federal Food, Drug, and Cosmetic Act ("the FD&C Act"), FDA regulations and other applicable regulations and policies provide incentives to manufacturers to create modified, non-infringing versions of a drug to facilitate the approval of an ANDA or other application for generic substitutes.
If our competitors are able to obtain orphan drug exclusivity for their products, we may not be able to have competing products approved by the applicable regulatory authority for a significant period of time. Regulatory authorities in some jurisdictions, including the E.U., U.K., and the U.S., may designate drugs for relatively small patient populations as orphan drugs.
If our competitors are able to obtain orphan drug exclusivity for their products, we may not be able to have competing products approved by the applicable regulatory authority for a significant period of time. Regulatory authorities in some jurisdictions, including the E.U., U.K., and U.S., may designate drugs for relatively small patient populations as orphan drugs.
We currently rely on the manufacturers of our products and product candidates to purchase from third-party suppliers the materials necessary to produce the compounds for our preclinical studies, clinical trials, and commercial supply and we rely, or will rely, on these other manufacturers for commercial distribution of our products and, if and when we obtain marketing approval, for any of our product candidates.
We currently rely on the manufacturers of our products and product candidates to purchase from third-party suppliers the materials necessary to produce the compounds for our preclinical studies, clinical trials, and commercial supply and we rely, or will rely, on these or other manufacturers for commercial distribution of our products and, if and when we obtain marketing approval, for any of our product candidates.
If we require substantial additional capital to fund our operations and we fail to obtain necessary financing, we may be unable to complete the development and commercialization of our products and development and commercialization of our product candidates. Our operations have consumed substantial amounts of cash.
If we require substantial additional capital to fund our operations and fail to obtain necessary financing, we may be unable to complete the development and commercialization of our products and development and commercialization of our product candidates. Our operations have consumed substantial amounts of cash.
If we are unable to raise additional capital in sufficient amounts, when required or on acceptable terms, we could also be required to: • significantly delay, scale back, or discontinue the development or the commercialization of our products or product candidates or one or more of our other research and development initiatives; • seek collaborators for Galafold ® , Pombiliti ™ + Opfolda ™ , or one or more of our current or future product candidates at an earlier stage than otherwise would be desirable, or on terms that are less favorable than might otherwise be available; • relinquish or license on unfavorable terms our rights to our technologies, products or product candidates that we otherwise would seek to develop or commercialize ourselves; • significantly curtail operations; or • enter into strategic partnerships on unfavorable terms, including a sale of our assets for less than full value.
If we are unable to raise additional capital in sufficient amounts, when required or on acceptable terms, we could also be required to: • significantly delay, scale back, or discontinue the development or commercialization of our products or product candidates or one or more of our other research and development initiatives; • seek collaborators for Galafold ® , Pombiliti ® + Opfolda ® , or one or more of our current or future product candidates at an earlier stage than otherwise would be desirable, or on terms that are less favorable than might otherwise be available; • relinquish or license on unfavorable terms our rights to our technologies, products or product candidates that we otherwise would seek to develop or commercialize ourselves; • significantly curtail operations; or • enter into strategic partnerships on unfavorable terms, including a sale of our assets for less than full value.
As part of the approval process for Galafold ® , FDA granted us a New Chemical Entity (“NCE”) exclusivity period during which other manufacturers’ applications for approval of generic versions of our product will not be approved.
As part of the approval process for Galafold ® , the FDA granted us a New Chemical Entity (“NCE”) exclusivity period during which other manufacturers’ applications for approval of generic versions of our product will not be approved.
The sale of generic versions of Galafold ® earlier than their patent expiration would have a significant negative effect on our revenues and results of operations. To seek approval for a generic version of a product having NCE status, a generic company may submit its ANDA to FDA four years after the branded product’s approval.
The sale of generic versions of Galafold ® earlier than their patent expiration would have a significant negative effect on our revenues and results of operations. To seek approval for a generic version of a product having NCE status, a generic company may submit its ANDA to the FDA four years after the branded product’s approval.
Third parties may own or control these patents or patent applications in the U.S. and abroad. These third parties could bring claims against us that would cause us to incur substantial expenses and, if successful against us, could cause us to pay substantial damages.
Third parties may own or control these patents or patent applications in the U.S. and abroad. These third parties could bring claims that would cause us to incur substantial expenses and, if successful against us, could cause us to pay substantial damages.
We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel, particularly in New Jersey and Philadelphia and their surrounding areas. Although we believe we offer competitive salaries and benefits, we may have to increase spending in order to retain personnel.
We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel, particularly in New Jersey, Philadelphia, and their surrounding areas. Although we believe we offer competitive salaries and benefits, we may have to increase spending in order to retain personnel.
The Global Risk Committee then uses this information to develop an Enterprise Risk Management Program, which identifies key risks, develops mitigation strategies for these risks, and reports material developments directly to the Audit and Compliance Committee on a quarterly basis, and to the full Board of Directors on a yearly basis.
The Global Risk Committee then uses this information to develop an Enterprise Risk Management Program, which identifies key risks, develops mitigation strategies for these risks, and reports material developments directly to the Audit and Compliance Committee on a quarterly basis, and the full Board of Directors on a yearly basis.
The review processes and the processes of regulatory authorities, including the FDA, EMA and PMDA, are extensive, lengthy, expensive, and uncertain, and such regulatory authorities may delay, limit, or deny the approval of any of our product candidates for many reasons, including, but not limited to: • our failure to demonstrate to the satisfaction of the applicable regulatory authorities that any of our product candidates, are safe and effective for a particular indication; • the results of clinical trials may not meet the level of statistical significance or other efficacy or safety parameters required by the applicable regulatory authorities for approval; • the applicable regulatory authority may disagree with the number, design, size, conduct, or implementation of our clinical trials or conclude that the data fail to meet statistical or clinical significance; • the applicable regulatory authority may not find the data from preclinical studies and clinical trials sufficient to demonstrate that the product candidate's clinical and other benefits outweigh its safety risks; • the applicable regulatory authority may disagree with our interpretation of data from preclinical studies or clinical trials, and may reject conclusions from preclinical studies or clinical trials, or determine that primary or secondary endpoints from clinical trials were not met, or reject safety conclusions from such studies or trials; • the applicable regulatory authority may not accept data generated at one or more of our clinical trial sites; • the applicable regulatory authority may determine that we did not properly oversee our clinical trials or follow the regulatory authority's advice or recommendations in designing and conducting our clinical trials; -27- Table of Contents • an advisory committee, if convened by the applicable regulatory authority, may recommend against approval of our application or may recommend that the applicable regulatory authority require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions, or even if an advisory committee, if convened, makes a favorable recommendation, the respective regulatory authority may still not approve the product candidate; • the applicable regulatory authority may only approve a limited label for less than the full indicated population, as a second line or rescue therapy, or impose other label restrictions; and • the applicable regulatory authority may identify deficiencies in the chemistry, manufacturing, and control sections of our application, our manufacturing processes, facilities, or analytical methods or those of our third-party contract manufacturers or be unable to complete any necessary manufacturing inspections of our third-party manufacturers which may lead to significant delays in the approval of our product candidates or to the rejection of our applications altogether.
The review processes and the processes of regulatory authorities, including the FDA, EMA and PMDA, are extensive, lengthy, expensive, and uncertain, and such regulatory authorities may delay, limit, or deny the approval of any of our product candidates for many reasons, including, but not limited to: • our failure to demonstrate to the satisfaction of the applicable regulatory authorities that any of our product candidates, are safe and effective for a particular indication; • the results of clinical trials may not meet the level of statistical significance or other efficacy or safety parameters required by the applicable regulatory authorities for approval; • the applicable regulatory authority may disagree with the number, design, size, conduct, or implementation of our clinical trials or conclude that the data fail to meet statistical or clinical significance; • the applicable regulatory authority may not find the data from preclinical studies and clinical trials sufficient to demonstrate that the product candidate's clinical and other benefits outweigh its safety risks; • the applicable regulatory authority may disagree with our interpretation of data from preclinical studies or clinical trials, and may reject conclusions from preclinical studies or clinical trials, determine that primary or secondary endpoints from clinical trials were not met, or reject safety conclusions from such studies or trials; • the applicable regulatory authority may not accept data generated at one or more of our clinical trial sites; -26- Table of Contents • the applicable regulatory authority may determine that we did not properly oversee our clinical trials or follow the regulatory authority's advice or recommendations in designing and conducting our clinical trials; • an advisory committee, if convened by the applicable regulatory authority, may recommend against approval of our application or may recommend that the applicable regulatory authority require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions, or even if an advisory committee, if convened, makes a favorable recommendation, the respective regulatory authority may still not approve the product candidate; • the applicable regulatory authority may only approve a limited label for less than the full indicated population, as a second line or rescue therapy, or impose other label restrictions; and • the applicable regulatory authority may identify deficiencies in the chemistry, manufacturing, and control sections of our application, our manufacturing processes, facilities, or analytical methods or those of our third-party contract manufacturers or be unable to complete any necessary manufacturing inspections of our third-party manufacturers which may lead to significant delays in the approval of our product candidates or to the rejection of our applications altogether.
Specifically, the anti-bribery provisions of the FCPA prohibit the willful use of the mails or any means of instrumentality of interstate commerce corruptly in furtherance of any offer, payment, promise to pay, or authorization of the payment of money or anything of value to any person, while knowing that all or a portion of such money or thing of value will be offered, given or promised, directly or indirectly, to a foreign official to influence the foreign official in his or her official capacity, induce the foreign official to do or omit to do an act in violation of his or her lawful duty, or to secure any improper advantage in order to assist in obtaining or retaining business for or with, or directing business to, any person; enforcement actions may be brought by the Department of Justice or the SEC; legislation has expanded the SEC’s power to seek disgorgement in all FCPA cases filed in federal court and extended the statute of limitations in SEC enforcement actions in intent-based claims, such as those under the FCPA, from five years to ten years; and • state and foreign equivalents of each of the above laws, including foreign anti-bribery and corruption laws and state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental payors, including private insurers; state laws which 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 restricting payments that may be made to healthcare providers; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Specifically, the anti-bribery provisions of the FCPA prohibit the willful use of the mail or any means of instrumentality of interstate commerce corruptly in furtherance of any offer, payment, promise to pay, or authorization of the payment of money or anything of value to any person, while knowing that all or a portion of such money or thing of value will be offered, given or promised, directly or indirectly, to a foreign official to influence the foreign official in his or her official capacity, induce the foreign official to do or omit to do an act in violation of his or her lawful duty, or to secure any improper advantage in order to assist in obtaining or retaining business for or with, or directing business to, any person; enforcement actions may be brought by the Department of Justice or the SEC; legislation has expanded the SEC’s power to seek disgorgement in all FCPA cases filed in federal court and extended the statute of limitations in SEC enforcement actions in intent-based claims, such as those under the FCPA, from five years to ten years; and • state and foreign equivalents of each of the above laws, including foreign anti-bribery and corruption laws and state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental payors, including private insurers; state laws which 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 restricting payments that may be made to healthcare providers; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
We have adopted a Code of Business Conduct and Ethics, a robust Enterprise Risk Management Program, have extensive Board of Directors oversight, and conduct comprehensive training, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
We have adopted a Code of Business Conduct and Ethics, implemented a robust Enterprise Risk Management Program, have extensive Board of Directors oversight, and conduct comprehensive training, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including: • restrictions on such products, manufacturers or manufacturing processes; • changes to or restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to implement a REMS; • requirements to conduct post-marketing studies or clinical trials; • warning letters, untitled letters or Form 483s; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • refusal to permit the import or export of our products; • product seizure; • injunctions; or • the imposition of civil or criminal penalties. -36- Table of Contents Non-compliance with E.U. and U.K. requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including: • restrictions on such products, manufacturers, or manufacturing processes; • changes to or restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to implement a REMS; • requirements to conduct post-marketing studies or clinical trials; • warning letters, untitled letters, or Form 483s; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution, or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • refusal to permit the import or export of our products; • product seizure; • injunctions; or • the imposition of civil or criminal penalties. -35- Table of Contents Non-compliance with E.U. and U.K. requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any product candidates or products that we may develop; -33- Table of Contents • injury to our reputation and significant negative media attention; • regulatory investigations, prosecutions or enforcement actions that could require costly recalls or product modifications; • withdrawal of clinical trial participants; • regulatory authorities placing ongoing clinical trials on clinical hold; • significant costs to defend the related litigation; • increased insurance costs, or an inability to maintain appropriate insurance coverage; • substantial monetary awards to trial participants or patients, including awards that substantially exceed our product liability insurance, which we would then be required to pay from other sources, if available, and would damage our ability to obtain liability insurance at reasonable costs, or at all, in the future; • loss of revenue; and • the inability to commercialize any products that we may develop.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any product candidates or products that we may develop; • injury to our reputation and significant negative media attention; -32- Table of Contents • regulatory investigations, prosecutions, or enforcement actions that could require costly recalls or product modifications; • withdrawal of clinical trial participants; • regulatory authorities placing ongoing clinical trials on clinical hold; • significant costs to defend the related litigation; • increased insurance costs or an inability to maintain appropriate insurance coverage; • substantial monetary awards to trial participants or patients, including awards that substantially exceed our product liability insurance, which we would then be required to pay from other sources, if available, and would damage our ability to obtain liability insurance at reasonable costs, or at all, in the future; • loss of revenue; and • the inability to commercialize any products that we may develop.
Undesirable side effects caused by our products, Galafold ® and Pombiliti ™ + Opfolda ™ , or product candidates could interrupt, delay or halt clinical trials and could result in the denial of regulatory approval by the FDA, EMA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing our products or product candidates, if approved, and generating revenues from their sale.
Undesirable side effects caused by our products, Galafold ® and Pombiliti ® + Opfolda ® , or product candidates could interrupt, delay or halt clinical trials and could result in the withdrawal or denial of regulatory approval by the FDA, EMA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing our products or product candidates, if approved, and generating revenues from their sale.
In addition, FDA and other regulatory bodies are continuing to evolve their guidance for gene therapy manufacturing and could impose rigorous requirements relating to the manufacturing and testing of clinical and commercial products that could add time, complexity and the risk that we or our manufacturing partners will be unable to meet these requirements.
In addition, the FDA and other regulatory bodies are continuing to evolve their guidance for gene therapy manufacturing and could impose rigorous requirements relating to the manufacturing and testing of clinical and commercial products that could add time, complexity, cost, and the risk that we or our manufacturing partners will be unable to meet these requirements.
Such failure could also result in product liability claims, product recalls, product seizures or withdrawals, delays or failures in testing or delivery, cost overruns or other problems that could seriously harm our business or profitability. The FDA and regulatory authorities in other jurisdictions require our contract manufacturers to comply with cGMP regulations.
Such failure could also result in product liability claims, product recalls, product seizures or withdrawals, delays or failures in testing or delivery, cost overruns or other problems that could seriously harm our business, profitability, or reputation. The FDA and regulatory authorities in other jurisdictions require our contract manufacturers to comply with cGMP regulations.
Additionally, our products, or the technologies or processes used to formulate or manufacture those products may now, or in the future, infringe the patent rights of third parties. It is also possible that third parties will obtain patent or other proprietary rights that might be necessary or useful for the development, manufacture or sale of our products.
Additionally, our products, or the technologies or processes used to formulate or manufacture those products may now, or in the future, infringe the patent rights of third parties. It is also possible that third parties will obtain patents or other proprietary rights that might be necessary or useful for the development, manufacture or sale of our products.
Regulatory authorities may determine that any of our products or product candidates are not effective or only moderately effective, or have undesirable or unintended side effects, toxicities, safety profiles or other characteristics that preclude us from obtaining marketing approval or that prevent or limit commercial use.
Regulatory authorities may determine that any of our products or product candidates are not effective or only moderately effective, or have undesirable or unintended side effects, toxicities, safety profiles or other characteristics that preclude us from obtaining marketing approval or that prevent or limit their commercial use.
We may also co-promote or out license our products or product candidates, if approved, in various markets with pharmaceutical and biotechnology companies in instances where we believe that a larger sales and marketing presence will expand the market or accelerate penetration.
We may also co-promote or out-license our products or product candidates, if approved, in various markets with pharmaceutical and biotechnology companies in instances where we believe that a larger sales and marketing presence will expand the market or accelerate penetration into the market.
Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers. Recently, the Inflation Reduction Act of 2022 (the "IRA") contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S.
Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers. The Inflation Reduction Act of 2022 (the "IRA") contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S.
For example, the FDA's requirements include submissions of safety and other post-marketing information and reports, registration requirements, Current Good Manufacturing Practices, or cGMP, requirements relating to manufacturing, quality control, quality assurance and complaints and corresponding maintenance of records and documents, requirements regarding the distribution of samples to healthcare professionals and recordkeeping.
For example, the FDA's requirements include submissions of safety and other post-marketing information and reports, registration requirements, Current Good Manufacturing Practices ("cGMP"), requirements relating to manufacturing, quality control, quality assurance and complaints and corresponding maintenance of records and documents, requirements regarding the distribution of samples to healthcare professionals and recordkeeping.
The FDA requires us to comply with standards, commonly referred to as Good Clinical Practices, or GCP, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected.
The FDA requires us to comply with standards, commonly referred to as Good Clinical Practices ("GCP"), for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, and confidentiality of trial participants are protected.
We or our partners may encounter product, packaging, equipment and process-related issues that may require refinement or resolution in order to successfully commercialize our products, proceed with planned clinical trials, or obtain regulatory approval for commercial marketing of our product candidates.
We or our partners may also encounter product, packaging, equipment and process-related issues that may require refinement or resolution in order to successfully commercialize our products, proceed with planned clinical trials, or obtain regulatory approval for commercial marketing of our product candidates.
However, this type of patent does not limit a competitor from making and marketing products that are identical to our products that is labeled for an indication that is outside of the patented method, or for which there is a substantial use in commerce outside the patented method.
This type of patent does not limit a competitor from making and marketing products that are identical to our products that is labeled for an indication that is outside of the patented method, or for which there is a substantial use in commerce outside the patented method.
Applicable regulations of both the EMA and E.U. member states also impose liability for failing to comply with fraud and abuse laws or improperly using information obtained in in the course of clinical trials with the EMA or other regulatory authorities; -37- Table of Contents • U.S. federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA") which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Applicable regulations of both the EMA and E.U. member states also impose liability for failing to comply with fraud and abuse laws or improperly using information obtained in in the course of clinical trials with the EMA or other regulatory authorities; -36- Table of Contents • U.S. federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA") which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • reliance on the third-party for regulatory compliance and quality assurance, including with their own vendors with which we do not have a contractual relationship; • limitations on supply availability resulting from capacity, scheduling constraints, and geographic of the third parties; • inability to manufacture product that meets the regulatory requirements for product approval; • inability to manufacture batches that meet specifications and quality standards; • inability to hire and retain the skilled workers necessary to manufacture our products; • inability to meet environmental sustainability requirements; • impact on our reputation in the marketplace if manufacturers of our products, once commercialized, fail to meet the demands of our customers; • the possible breach of the manufacturing agreement by the third-party; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; • the high cost of manufacturing processes and raw materials; and • the possible termination or nonrenewal of the agreement by the third-party at a time that is costly or inconvenient for us.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: -41- Table of Contents • reliance on the third party for regulatory compliance and quality assurance, including with their own vendors with which we do not have a contractual relationship; • limitations on supply availability resulting from capacity, scheduling constraints, and geographic of the third parties; • inability to manufacture product that meets the regulatory requirements for product approval; • inability to manufacture batches that meet specifications and quality standards; • inability to hire and retain the skilled workers necessary to manufacture our products; • inability to meet environmental sustainability requirements; • impact on our reputation in the marketplace if manufacturers of our products, once commercialized, fail to meet the demands of our customers; • the possible breach of the manufacturing agreement by the third party; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; • the high cost of manufacturing processes and raw materials; and • the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.
Moreover, there are complex regulatory, tax, labor and other legal requirements imposed by the E.U., U.K., and many of the individual countries in Europe, Asia and Latin America with which we will need to comply.
Moreover, there are complex regulatory, tax, labor, environmental and other legal requirements imposed by the E.U., U.K., and many of the individual countries in Europe, Asia, and Latin America with which we will need to comply.
Following the receipt of marketing approval of our products or any product candidates, the products may become subject to unfavorable pricing regulations, third-party coverage and reimbursement practices or healthcare reform initiatives, which would harm our business.
Following the receipt of marketing approval of our products or any product candidates, the products may become subject to unfavorable pricing regulations, third-party coverage, reimbursement practices or healthcare reform initiatives, which would harm our business.
In the U.S., after an NDA is approved, the product covered thereby becomes a "listed drug" which can, in turn, be cited by potential competitors in support of approval of an abbreviated NDA, or ANDA.
In the U.S., after an NDA is approved, the product covered thereby becomes a "listed drug," which can, in turn, be cited by potential competitors in support of approval of an abbreviated NDA ("ANDA").
Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, allow our competitors to bring products to market before we do, or impair our ability to successfully commercialize our product candidates, and so may harm our business and results of operations. -40- Table of Contents If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, allow our competitors to bring products to market before we do, or impair our ability to successfully commercialize our product candidates, and so may harm our business and results of operations. -39- Table of Contents If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
Our products, Galafold ® and Pombiliti ™ + Opfolda ™ , and product candidates and the activities associated with their development and commercialization, including their testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, commercialization and reimbursement are subject to comprehensive regulation by the European Medicines Agency (“EMA”), the Pharmaceutical and Medical Devices Agency (“PMDA”), the Food and Drug Administration (“FDA”), and other regulatory agencies in the U.S. and by comparable authorities in other countries.
Our commercial products, Galafold ® and Pombiliti ® + Opfolda ® , any product candidates and the activities associated with their development and commercialization, including their testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, commercialization and reimbursement are subject to comprehensive regulation by the European Medicines Agency (“EMA”), the Pharmaceutical and Medical Devices Agency (“PMDA”), the Food and Drug Administration (“FDA”), and other regulatory agencies in the U.S. and by comparable authorities in other countries.
If our sales of Galafold ® were to decrease, or such sales were substantially or completely displaced in the market, or if we are unable to achieve and maintain sufficient market acceptance of Galafold ® by physicians, patients, third-party payors and others in the medical community, or if we fail to receive commercial approval in any additional jurisdictions, it could have a material adverse effect on our business, financial condition and results of operations.
If our sales of Our Commercial Products were to decrease, or such sales were substantially or completely displaced in the market, or if we are unable to achieve and maintain sufficient market acceptance of Our Commercial Products by physicians, patients, third-party payors and others in the medical community, or if we fail to receive commercial approval in any additional jurisdictions, it could have a material adverse effect on our business, financial condition and results of operations.
We are also aware of other enzyme replacement and substrate reduction therapies in development by third parties for Fabry and Pompe, as well as potential gene therapies for both Fabry and Pompe and our other product candidates. -30- Table of Contents Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
We are also aware of other enzyme replacement and substrate reduction therapies in development by third parties for Fabry and Pompe, as well as potential gene therapies for both Fabry and Pompe and our other product candidates. -29- Table of Contents Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
If the FDA or other applicable regulatory authorities approve generic or biosimilar products that compete with our products or any of our product candidates, it could reduce our sales of our products or those product candidates.
If the FDA or other applicable regulatory authorities approve generic or biosimilar products that compete with our products or any of our product candidates, it could reduce sales of our products or product candidates.
The FDA may impose further requirements or restrictions on the distribution or use of any of our other product candidates as part of a Risk Evaluation and Mitigation Strategies ("REMS") plan. Physicians may nevertheless prescribe such products to their patients in a manner that is inconsistent with the approved label provided the company did not promote such use.
The FDA may impose further requirements or restrictions on the distribution or use of any of our product candidates, if approved, as part of a Risk Evaluation and Mitigation Strategies ("REMS") plan. Physicians may nevertheless prescribe such products to their patients in a manner that is inconsistent with the approved label provided the company did not promote such use.
Any change in a CRO during an ongoing preclinical development activity or clinical trial could seriously delay that trial and potentially compromise the results of the activity or trial. -45- Table of Contents We may not be successful in maintaining or establishing collaborations, which could adversely affect our ability to develop and, particularly in international markets, commercialize products.
Any change in a CRO during an ongoing preclinical development activity or clinical trial could seriously delay that trial and potentially compromise the results of the activity or trial. -43- Table of Contents We may not be successful in maintaining or establishing collaborations, which could adversely affect our ability to develop and, particularly in international markets, commercialize products.
Litigation may be necessary to defend against these claims. -57- Table of Contents In addition, while we typically require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own.
Litigation may be necessary to defend against these claims. -55- Table of Contents In addition, while we typically require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own.
We rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators and collaboration partners to perform these functions. Any of these third parties may terminate their engagements with us at any time. If we need to enter into alternative arrangements, it would delay our product development activities.
We rely on third parties, such as contract research organizations ("CROs"), clinical data management organizations, medical institutions, clinical investigators, and collaboration partners to perform these functions. Any of these third parties may terminate their engagements with us at any time. If we need to enter into alternative arrangements, it would delay our product development activities.
As these tensions continue to rise, more targeted approaches by the U.S. or PRC governments on certain products, industries or companies (including WuXi, a sole supplier of one of our products) could significantly impact our ability to effectively manufacture and distribute our products, including Pombiliti ™ + Opfolda ™ , materially impacting our ability to meet patient demands or financial forecasts.
As these tensions continue to rise, more targeted approaches by the U.S. or Chinese governments on certain products, industries or companies (including WuXi, a sole supplier of one of our products) could significantly impact our ability to effectively manufacture and distribute our products, including Pombiliti ® + Opfolda ® , materially impacting our ability to meet patient demands or financial forecasts.
Participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, potential liability for the failure to report such prices in an accurate and timely manner, and potentially limit our ability to offer certain marketplace discounts; -38- Table of Contents • U.S.
Participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, potential liability for the failure to report such prices in an accurate and timely manner, and potentially limit our ability to offer certain marketplace discounts; -37- Table of Contents • U.S.
We expect to continue to incur significant costs in the foreseeable future as we: • continue our development and commercialization of our products and seek regulatory approvals for our product candidates in the U.S., the E.U., U.K., Japan and other foreign countries, as applicable; • conduct additional clinical trials to support the full approval of Galafold ® in the U.S. and post-approval commitments or trials; • continue communicating with the EMA, as necessary, regarding post-marketing requirements and clinical trials for Galafold ® ; • continue to or initiate the regulatory submission process for marketing approval of Galafold ® and Pombiliti ™ + Opfolda ™ outside of the U.S. and E.U. and other foreign jurisdictions where approved, as applicable; • build and maintain our commercial infrastructure so that it is capable of supporting product sales, marketing and distribution of Galafold ® and Pombiliti ™ + Opfolda ™ , as well as our other product candidates in Europe, Japan and the U.S. or other territories in which we have received or may receive regulatory approval; • continue our next-generation product research; and • continue our rigorous prosecution and defense of our patent portfolio.
We expect to continue to incur significant costs in the foreseeable future as we: • continue our development and commercialization of our products and seek regulatory approvals for our product candidates in the U.S., E.U., U.K., Japan and other foreign countries, as applicable; • conduct additional clinical trials to support the full approval of Galafold ® in the U.S. and post-approval commitments or trials in the E.U. and other geographies; -46- Table of Contents • continue communicating with the EMA, as necessary, regarding post-marketing requirements and clinical trials for Galafold ® ; • continue to or initiate the regulatory submission process for marketing approval of Galafold ® and Pombiliti ® + Opfolda ® outside of the U.S. and E.U. and other foreign jurisdictions where approved, as applicable; • build and maintain our commercial infrastructure so that it is capable of supporting product sales, marketing and distribution of Galafold ® and Pombiliti ® + Opfolda ® , as well as our other product candidates in Europe, Japan, the U.S., or other territories in which we have received or may receive regulatory approval; • continue our next-generation product research; and • continue our rigorous prosecution and defense of our patent portfolio.
Factors that may inhibit our efforts to successfully commercialize Galafold ® , Pombiliti ™ + Opfolda ™ , or our product candidates if and when they are approved by regulatory authorities, on our own include: • our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to adequate numbers of physicians to prescribe any future products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; • unforeseen costs and expenses associated with creating an independent sales and marketing organization; • misconduct by independent sales and marketing organizations that expose us to fines, penalties and other restrictions on our ability to effectively market and sell our products; and -28- Table of Contents • efforts by our competitors to commercialize products at or about the time when our product candidates would be coming to market.
Factors that may inhibit our efforts to successfully commercialize Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates if and when they are approved by regulatory authorities, on our own include: • our inability to recruit, train, and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to adequate numbers of physicians to prescribe our products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; • unforeseen costs and expenses associated with creating an independent sales and marketing organization; -27- Table of Contents • misconduct by independent sales and marketing organizations that expose us to fines, penalties and other restrictions on our ability to effectively market and sell our products; and • efforts by our competitors to commercialize products at or about the time when our product candidates would be coming to market.
If our common stock is delisted by NASDAQ, we could face significant material adverse consequences, including: • a limited availability of market quotations for our securities; • reduced liquidity with respect to our securities; • a determination that our shares are a "penny stock," which will require brokers trading in our shares to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for our shares; • a limited amount of news and analyst coverage for our company; and • a decreased ability to issue additional securities or obtain additional financing in the future.
If our common stock is delisted by NASDAQ, we could face significant material adverse consequences, including: • a limited availability of market quotations for our securities; • reduced liquidity with respect to our securities; • a determination that our shares are a "penny stock," which will require brokers trading in our shares to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for our shares; • a limited amount of news and analyst coverage for our company; and -65- Table of Contents • a decreased ability to issue additional securities or obtain additional financing in the future.
Many U.S.-based biopharmaceutical companies have found the process of marketing their own products in Europe and other international geographies to be very challenging. -31- Table of Contents In addition, Pombiliti ™ is currently manufactured in the People's Republic of China (“PRC”) by WuXi Biologics Co., Ltd. (“WuXi”).
Many U.S.-based biopharmaceutical companies have found the process of marketing their own products in Europe and other international geographies to be very challenging. -30- Table of Contents In addition, Pombiliti ® is currently manufactured in the People's Republic of China (“PRC”) by WuXi Biologics Co., Ltd. (“WuXi”).
If we, or our suppliers, third-party contractors, clinical investigators or collaborators are slow to adapt, or are unable to adapt, to changes in existing regulatory requirements or adoption of new regulatory requirements or policies, we or our collaborators may lose marketing approval for our products when and if any of them are approved, resulting in decreased revenue from milestones, product sales or royalties.
If we, our suppliers, third-party contractors, clinical investigators, or collaborators are slow to adapt, or are unable to adapt, to changes in existing regulatory requirements or adoption of new regulatory requirements or policies, we or our collaborators may lose marketing approval for our products when and if approved, resulting in decreased revenue from milestones, product sales, or royalties.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • we or our licensors were the first to make the inventions covered by each of our pending patent applications; • we or our licensors were the first to file patent applications for these inventions; • others will not independently develop similar or alternative technologies or duplicate any of our technologies; • any patents issued to us or our licensors will provide a basis for commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • licenses from other third parties will not be required to commercialize patented products; • we will develop additional proprietary technologies that are patentable; • we will file patent applications for new proprietary technologies promptly or at all; • our patents will not expire prior to or shortly after commencing commercialization of a product; • the patents of others will not have a negative effect on our ability to do business; • patent authorities will not identify deficiencies in our patent applications and refuse to grant our patents; or • outcome of any patent litigation, including Hatch-Waxman litigation involving Galafold ® , or any possible future litigation involving Pombiliti ™ + Opfolda ™ , will demonstrate that our patents are valid and enforceable. -53- Table of Contents In addition, we cannot be assured that any of our pending patent applications will result in issued patents.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • we or our licensors were the first to make the inventions covered by each of our pending patent applications; • we or our licensors were the first to file patent applications for these inventions; • others will not independently develop similar or alternative technologies or duplicate any of our technologies; • any patents issued to us or our licensors will provide a basis for commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • licenses from other third parties will not be required to commercialize patented products; -51- Table of Contents • we will develop additional proprietary technologies that are patentable; • we will file patent applications for new proprietary technologies promptly or at all; • our patents will not expire prior to or shortly after commencing commercialization of a product; • the patents of others will not have a negative effect on our ability to do business; • patent authorities will not identify deficiencies in our patent applications and refuse to grant our patents; or • outcome of any patent litigation, including Hatch-Waxman litigation involving Galafold ® , or any possible future litigation involving Pombiliti ® + Opfolda ® , will demonstrate that our patents are valid and enforceable.
Moreover, physicians may prescribe such competitive identical products for indications other than the one for which the products have been approved, or off-label indications, that are covered by the applicable patents. Although such off-label prescriptions may infringe or induce infringement of method of use patents, the practice is common and such infringement is difficult to prevent or prosecute.
Additionally, physicians may prescribe such competitive identical products for indications other than the one for which the products have been approved, or off-label indications, that are covered by the applicable patents. Although such off-label prescriptions may infringe or induce infringement of method of use patents, the practice is common and such infringement is difficult to prevent or prosecute.
We have established our own sales and marketing capabilities to promote Galafold ® in Europe, Japan, the U.S. and other foreign jurisdictions with a targeted sales force and have leveraged these resources to support the launch of Pombiliti ™ + Opfolda ™ in those same jurisdictions. We anticipate using these capabilities to support other product candidates if approved.
We have established our own sales and marketing capabilities to promote Galafold ® in Europe, Japan, the U.S., and other foreign jurisdictions with a targeted sales force and have leveraged these resources to support the ongoing commercial launch of Pombiliti ® + Opfolda ® in those same jurisdictions. We anticipate using these capabilities to support other product candidates if approved.
Thus, after the introduction of a generic competitor, a significant percentage of the sales of any branded product are typically lost to the generic product. Accordingly, competition from generic equivalents to our products or product candidates, including Galafold ® , would substantially limit our ability to generate revenues or achieve profitability with a negative impact on continued operations.
Thus, after the introduction of a generic competitor, a significant percentage of the sales of any branded product are typically lost to the generic product. Accordingly, competition from generic equivalents to our products or product candidates would substantially limit our ability to generate revenues or achieve profitability with a negative impact on continued operations.
Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violates: • FDA or similar regulations of foreign regulatory authorities, including those laws requiring the reporting of true, complete and accurate information to such authorities; • manufacturing standards; • federal and state healthcare fraud and abuse laws and regulations, anti-bribery and corruption laws, anti-discrimination and harassment laws, privacy and similar laws and regulations established and enforced by foreign regulatory authorities; -59- Table of Contents • laws that require the reporting of financial information or data accurately; or • laws requiring the timely and accurate disclosure of material information to investors and analysts.
Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violates: • the FDA or similar regulations of foreign regulatory authorities, including those laws requiring the reporting of true, complete and accurate information to such authorities; • manufacturing standards; • federal and state healthcare fraud and abuse laws and regulations, anti-bribery and corruption laws, anti-discrimination and harassment laws, privacy and similar laws and regulations established and enforced by foreign regulatory authorities; • laws that require the reporting of financial information or data accurately; or • laws requiring the timely and accurate disclosure of material information to investors and analysts.
Additionally, trade policies and geopolitical disputes (including as a result of China-Taiwan relations) and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially adversely affect our business, particularly if these measures occur in regions where we source our components or raw materials.
Additionally, trade policies and geopolitical disputes (including as a result of PRC-Taiwan relations) and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially adversely affect our business, particularly if these measures occur in regions where we source our components or raw materials.
In addition to the factors discussed in this Annual Report on Form 10-K, these factors include: • the success of competitive products or technologies; • regulatory actions with respect to our products or product candidates or our competitors' products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the outcome of any patent infringement or other litigation that may be brought against us or we may bring against others; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; -64- Table of Contents • results of clinical trials of our product candidates or those of our competitors; • regulatory or legal developments in the E.U., U.K., U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to our product or any of our product candidates or clinical development programs; • actual or anticipated variations in our quarterly operating results; • the number and characteristics of our efforts to in-license or acquire additional product candidates or products; • introduction of new products or services by us or our competitors; • failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or those of companies that are perceived to be similar to us; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • changes in accounting practices; • lawsuits and other claims asserted against us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; • publication of research reports about us, our competitors or our industry, or positive or negative recommendations or withdrawal of research coverage by securities or industry analysts; • other events or factors, many of which are beyond our control; and • the other factors described in this "Risk Factors" section.
In addition to the factors discussed in this Annual Report on Form 10-K, these factors include: • the success of competitive products or technologies; • regulatory actions with respect to our products or product candidates or our competitors' products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the outcome of any patent infringement or other litigation that may be brought against us or we may bring against others; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • results of clinical trials of our product candidates or those of our competitors; • regulatory or legal developments in the E.U., U.K., U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to our product or any of our product candidates or clinical development programs; • actual or anticipated variations in our quarterly operating results; • the number and characteristics of our efforts to in-license or acquire additional product candidates or products; • introduction of new products or services by us or our competitors; • failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or those of companies that are perceived to be similar to us; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • changes in accounting practices; • lawsuits and other claims asserted against us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; • publication of research reports about us, our competitors or our industry, or positive or negative recommendations or withdrawal of research coverage by securities or industry analysts; • other events or factors, many of which are beyond our control; and • the other factors described in this "Risk Factors" section. -64- Table of Contents In addition, the stock market in general, and pharmaceutical and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.
Galafold ® , Pombiliti ™ + Opfolda ™ , and any of our product candidates that may be approved in the future for commercialization in the E.U., U.K. or in other foreign countries are or will be subject to additional risks related to international operations or entering into international business relationships, including: • different regulatory requirements for maintaining approval of drugs in foreign countries; • reduced protection for contractual and intellectual property rights in some countries; • unexpected changes in taxes, tariffs, trade barriers and regulatory requirements; • economic weakness, including rising interest rates, inflation and political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • our ability, and our commercialization partners ability, to comply with local laws, rules and regulations, including those relating to modern slavery; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • workforce uncertainty in countries where labor unrest is more common than in the U.S.; • noncompliance with the U.S.
Galafold ® , Pombiliti ® + Opfolda ® , and any of our product candidates that may be approved in the future for commercialization in the E.U., U.K. or other foreign countries are or will be subject to additional risks related to international operations or entering into international business relationships, including: • different regulatory requirements for maintaining approval of drugs in foreign countries; • reduced protection for contractual and intellectual property rights in some countries; • unexpected changes in taxes, tariffs, trade barriers and regulatory requirements, particularly in light of a new presidential administration in the U.S.; • economic weakness, including rising interest rates, inflation and political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • our ability, and our commercialization partners ability, to comply with local laws, rules and regulations, including those relating to modern slavery; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • workforce uncertainty in countries where labor unrest is more common than in the U.S.; • noncompliance with the U.S.
We also expect that the Affordable Care Act, as well as other healthcare reform measures that have and may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for our products and product candidates, if approved.
We also expect that the Affordable Care Act, as well as other healthcare reform measures that have and may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the prices that we receive for our products and product candidates, if approved.
The FDA has very broad enforcement authority, and failure to abide by these regulations can result in penalties, including the issuance of a warning letter directing a company to correct deviations from regulatory standards and enforcement actions that can include seizures, injunctions and criminal prosecution.
The FDA has very broad enforcement authority, and failure to abide by these regulations can result in penalties, including withdrawal of approval, the issuance of a warning letter directing a company to correct deviations from regulatory standards and enforcement actions that can include seizures, injunctions and criminal prosecution.
Our key business partners, manufacturers and vendors face these same risks and a successful attack on their systems could have a similar negative impact to our business and operations. Moreover, new SEC reporting requirements now mandate specific disclosures in the event of a material cybersecurity incident.
Our key business partners, manufacturers and vendors face these same risks and a successful attack on their systems could have a similar negative impact to our business and operations. Moreover, SEC reporting requirements mandate specific disclosures in the event of a material cybersecurity incident.
Further, the success of Galafold ® will depend on a number of factors, including the following: • obtaining a sufficiently broad label in each territory that would not unduly restrict patient access; • obtaining additional foreign approvals for Galafold ® ; • continuing to build and maintain an infrastructure capable of supporting product sales, marketing, and distribution of Galafold ® in the U.S., Europe, Japan and other territories where we pursue commercialization directly; • maintaining commercial manufacturing arrangements with third-party manufacturers; • maintaining commercial distribution agreements with third-party distributors; • launching commercial sales of Galafold ® , where approved, whether alone or in collaboration with others; • acceptance of Galafold ® , where approved, by patients, the medical community and third-party payors; • effectively competing with other therapies, including potential generics and gene therapies; -26- Table of Contents • successfully identifying new patients who could benefit from Galafold ® ; • a continued acceptable safety profile of Galafold ® ; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity; • protecting and enforcing our rights in our intellectual property portfolio; and • obtaining and maintaining a commercially viable price.
Further, the success of Our Commercial Products will depend on a number of factors, including the following: • obtaining a sufficiently broad label in each territory that would not unduly restrict patient access; • obtaining additional foreign approvals for Our Commercial Products; • continuing to build and maintain an infrastructure capable of supporting product sales, marketing, and distribution of Our Commercial Products in the U.S., Europe, Japan and other territories where we pursue commercialization directly; • maintaining commercial manufacturing arrangements with third-party manufacturers; • maintaining commercial distribution agreements with third-party distributors; • launching commercial sales of Our Commercial Products, where approved, whether alone or in collaboration with others; • obtaining acceptance of Our Commercial Products, where approved, by patients, the medical community, and third-party payors; -25- Table of Contents • competing effectively with other therapies, including competitor products, potential generics and gene therapies; • identifying new patients who could benefit from Our Commercial Products successfully; • continuing an acceptable safety profile of Our Commercial Products; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity; • protecting and enforcing our rights in our intellectual property portfolio; and • obtaining and maintaining a commercially viable price.
We may experience ownership changes in the future as a result of shifts in our stock ownership some of which are outside our control. We completed a detailed study of the NOLs for the tax year 2023 and determined that there was not an ownership change in excess of 50%.
We may experience ownership changes in the future as a result of shifts in our stock ownership some of which are outside our control. We completed a detailed study of the NOLs for the tax year 2024 and determined that there was not an ownership change in excess of 50%.
If we are unable to establish and maintain sales and marketing capabilities or enter into agreements with third parties to market and sell our products or product candidates, if approved, we may not be successful in commercializing Galafold ® , Pombiliti ™ + Opfolda ™ , or any product candidate if and when they are approved.
If we are unable to establish and maintain sales and marketing capabilities or enter into agreements with third parties to market and sell our products or, if approved, our product candidates, we may not be successful in commercializing Galafold ® , Pombiliti ® + Opfolda ® , or any product candidate.
Failure to comply with applicable FDA requirements and restrictions also may subject a company to adverse publicity and enforcement action by the FDA, the U.S. Department of Justice ("DOJ") or the Office of the Inspector General of the U.S. Department of Health and Human Services ("HHS") as well as state authorities.
Failure to comply with applicable FDA requirements and restrictions also may subject a company to adverse publicity and enforcement action by the FDA, the U.S. Department of Justice ("DOJ"), the Office of the Inspector General of the U.S. Department of Health and Human Services ("HHS"), or state authorities.
While we have robust detection, mitigation, response and recovery protocols in place, there is no guarantee that these will be effective in preventing disruptions to our operations and adequately safeguard confidential, propriety or sensitive information from misappropriation or corruption.
While we have robust detection, mitigation, response and recovery protocols in place, there is no guarantee that these will be effective in preventing disruptions to our operations and adequately safeguard confidential, proprietary or sensitive information from misappropriation or corruption.
There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing our products and product candidates. The majority of our preclinical, clinical and commercial products, including Galafold ® and Pombiliti ™ , are manufactured by single source third-party manufacturers.
There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing our products and product candidates. The majority of our product candidates and commercial products, including Galafold ® and Pombiliti ® , are manufactured by single source third party manufacturers.
Although the European Commission, PMDA and FDA have granted approval for Galafold ® , for the treatment of adults with a confirmed diagnosis of Fabry disease and who have an amenable genetic variant, as well as Pombiliti ™ + Opfolda ™ for the treatment of adults with Pompe disease, and we are generating product sales, we continue to incur significant research, development, commercialization and other expenses related to our ongoing operations.
Although the European Commission, PMDA, FDA, and other regulatory authorities have granted approval for Galafold ® , for the treatment of adults with a confirmed diagnosis of Fabry disease and who have an amenable genetic variant, as well as Pombiliti ® + Opfolda ® for the treatment of adults with Pompe disease, and we are generating product sales, we continue to incur significant research, development, commercialization, manufacturing, and other expenses related to our ongoing operations.
Our inability to generate funds sufficient to satisfy our debt payment obligations or remain in compliance with the debt covenants may result in such obligations being accelerated by our lenders, which would likely have a material adverse effect on our business, financial condition and results of operations. Foreign currency exchange rate fluctuations could harm our financial results.
Our inability to generate sufficient funds to satisfy our debt payment obligations or remain in compliance with the debt covenants may result in such obligations being accelerated by our lenders, which would likely have a material adverse effect on our business, financial condition and results of operations. -49- Table of Contents Foreign currency exchange rate fluctuations could harm our financial results.
Investors who are focused on ESG matters may seek enhanced ESG disclosures or to implement policies adverse to our business, and there can be no assurances that stockholders will not advocate, via proxy contests, media campaigns or other public or private means, for us to make corporate governance changes or engage in certain corporate actions.
Investors who are focused on these matters may seek enhanced sustainability disclosures or to implement policies adverse to our business, and there can be no assurances that stockholders will not advocate, via proxy contests, media campaigns or other public or private means, for us to make corporate governance changes or engage in certain corporate actions.
We do not maintain "key person" insurance on Mr. Campbell or on any of our other key personnel. Recruiting and retaining qualified scientific, clinical and sales and marketing personnel will also be critical to our success.
We do not maintain "key person" insurance on Mr. Campbell or on any of our other key personnel. Recruiting and retaining qualified scientific, clinical, technical operations, and sales and marketing personnel will also be critical to our success.
We may not identify or complete these transactions in a timely manner, on a cost-effective basis, or at all despite a substantial outlay of resources in pursuing such -62- Table of Contents transactions, and we may not realize the anticipated benefits of any such transaction, any of which could have a detrimental effect on our financial condition, results of operations, and cash flows.
We may not identify or complete these transactions in a timely manner, on a cost-effective basis, or at all despite a substantial outlay of resources in pursuing such transactions, and we may not realize the anticipated benefits of any such transaction, any of which could have a detrimental effect on our financial condition, results of operations, and cash flows.
Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or product candidate or could substantially increase the costs and expenses of commercializing the product or product candidate, if approved, which in turn could delay or prevent us from generating significant revenues from its sale and limiting our ability to meet our financial guidance, debt covenants or adversely affect our reputation. -35- Table of Contents Any product or product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market and we may be subject to penalties or other enforcement actions if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products or our product candidates, when and if any of them are approved.
Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or product candidate or could substantially increase the costs and expenses of commercializing the product or product candidate, if approved, which in turn could delay or prevent us from generating significant revenues from its sale and limiting our ability to meet our financial guidance, debt covenants or adversely affect our reputation. -34- Table of Contents Any product or product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market and we may be subject to penalties or other enforcement actions if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products or our product candidates, if approved.
If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates.
If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical development activities in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates.
We believe that any disclosure controls and procedures, no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. -52- Table of Contents These inherent limitations reflect the reality that judgments can be faulty, and that breakdowns can occur because of simple error or mistake.
We believe that any disclosure controls and procedures, no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. These inherent limitations reflect the reality that judgments can be faulty, and that breakdowns can occur because of simple error or mistake.
Our disclosure controls and procedures are designed to reasonably assure that information required to be disclosed by us in reports we file or submit under the Exchange Act is accumulated and communicated to management, recorded, processed, summarized and reported within the time periods specified in the rules and forms of the Securities and Exchange Commission.
Our disclosure controls and procedures are designed to reasonably assure that information required to be disclosed by us in reports we file or submit under the Exchange Act is accumulated and communicated to management, recorded, processed, summarized and reported within the time periods specified in the rules and forms of the SEC.
Accordingly, other manufacturers potentially could develop and seek FDA approval of "biosimilar" products at some point in the future, including a biosimilar of Pombiliti ™ or any other product we develop or acquire that is approved under a BLA. -34- Table of Contents Our competitors may be able to develop and commercialize their products, including products identical to ours, in any ex-U.S. jurisdiction in which we are unable to obtain, maintain, or enforce our patent claims.
Accordingly, other manufacturers potentially could develop and seek FDA approval of "biosimilar" products at some point in the future, including a biosimilar of Pombiliti ® or any other product we develop or acquire that is approved under a BLA. -33- Table of Contents Our competitors may be able to develop and commercialize their products, including products identical to ours, in any non-U.S. jurisdiction in which we are unable to obtain, maintain, or enforce our patent claims.
The labeling, advertising, promotion, marketing and distribution of a drug, biologic, or gene therapy product also must be in compliance with FDA requirements which include, among others, promotional activities, standards and regulations for direct-to-consumer advertising, promotional activities involving the internet, and industry sponsored scientific and educational activities.
The labeling, advertising, promotion, marketing and distribution of a drug, biologic, or gene therapy product also must be in compliance with FDA requirements which include, among others, promotional activities, standards and regulations for direct-to-consumer advertising, promotional activities involving the internet and social media platforms, and industry sponsored scientific and educational activities.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeTo facilitate the success of the Company’s cybersecurity risk management program, multidisciplinary teams throughout the Company are deployed to address cybersecurity threats and to respond to cybersecurity incidents.
Biggest changeTo facilitate the success of the Company’s cybersecurity risk management program, multidisciplinary teams, comprised of our cybersecurity experts, are deployed throughout the Company to identify and address cybersecurity threats and to respond to cybersecurity incidents.
Technical Safeguards: The Company deploys technical safeguards that are designed to protect the Company’s information systems from cybersecurity threats, including firewalls, intrusion prevention and detection systems, anti-malware functionality and access controls, 24x7 security monitoring, and other controls which are evaluated and improved through vulnerability assessments and cybersecurity threat intelligence. • Incident Response and Recovery Planning: The Company has established and maintains systematic incident response and recovery plans that address the Company’s response to a cybersecurity incident, and such plans are tested and evaluated on a periodic basis. • Third-Party Risk Management: The Company maintains a systematic, risk-based approach to identifying and overseeing cybersecurity risks presented by third parties, including vendors, service providers and other external users of the Company’s systems, as well as the systems of third parties that could adversely impact our business in the event of a cybersecurity incident affecting those third-party systems. • Education and Awareness: The Company provides regular, mandatory cybersecurity training for all personnel as a means to equip the Company’s workforce with effective tools to recognize, address and communicate potential or actual threats to the Company’s cybersecurity systems.
Technical Safeguards: The Company deploys technical safeguards that are designed to protect the Company’s information systems from cybersecurity threats, including firewalls, intrusion prevention and detection systems, anti-malware functionality and access controls, 24x7 security monitoring, and other controls which are evaluated and improved through vulnerability assessments and cybersecurity threat intelligence. • Incident Response and Recovery Planning: The Company has established and maintains systematic incident response and recovery plans that address the Company’s response to a cybersecurity incident, and such plans are tested and evaluated on a periodic basis. • Third-Party Risk Management: The Company maintains a systematic, risk-based approach to identifying and overseeing cybersecurity risks presented by third parties, including vendors, service providers and other external users -67- Table of Contents of the Company’s systems, as well as the systems of third parties that could adversely impact our business in the event of a cybersecurity incident affecting those third-party systems. • Education and Awareness: The Company provides regular, mandatory cybersecurity training for all personnel as a means to equip the Company’s workforce with effective tools to recognize, address and communicate potential or actual threats to the Company’s cybersecurity systems.
These efforts include a wide range of activities, including audits, assessments, tabletop exercises, threat modeling, vulnerability testing and other exercises focused on evaluating the -68- Table of Contents effectiveness of our cybersecurity measures and planning.
These efforts include a wide range of activities, including audits, assessments, tabletop exercises, threat modeling, vulnerability testing and other exercises focused on evaluating the effectiveness of our cybersecurity measures and planning.
Additionally, cybersecurity is also a standing agenda topic for the Global Risk Committee, with periodic updates to the Executive Committee and Senior Leadership Team.
Additionally, cybersecurity is also a standing agenda topic for the Global Risk Committee, with periodic updates to the Executive Committee.
The CIO holds a Certified Information Systems Security Professional certification, an undergraduate degree in engineering, an MBA and a PhD in engineering.
The CIO holds a Certified Information Systems Security Professional certification, an undergraduate degree in engineering, an MBA and a PhD in engineering. -68- Table of Contents

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. PROPERTIES The following table contains information about our current significant leased properties as of December 31, 2023.
Biggest changeItem 2. PROPERTIES The following table contains information about our current significant leased properties as of December 31, 2024.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. LEGAL PROCEEDINGS -69- Table of Contents The information called for by this item is incorporated herein by reference to the information set forth in Note 15 “Legal Proceedings” of the Notes to Consolidated Financial Statements included in Item 8 of this Report. Item 4. MINE SAFETY DISCLOSURES None. -70- Table of Contents PART II
Biggest changeItem 3. LEGAL PROCEEDINGS The information called for by this item is incorporated herein by reference to the information set forth in Note 15 “Legal Proceedings” of the Notes to Consolidated Financial Statements included in Item 8 of this Report. Item 4. MINE SAFETY DISCLOSURES None. -69- Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThe stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. 12/31/2018 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 Amicus Therapeutics, Inc. $100 $102 $241 $121 $125 $149 NASDAQ Composite $100 $135 $194 $236 $157 $223 NASDAQ Biotechnology $100 $124 $156 $155 $137 $146 The stock price performance included in this graph is not necessarily indicative of future stock price performance. -71- Table of Contents Issuer Purchases of Equity Securities The following table provides certain information with respect to purchase of our common stock during the three months ended December 31, 2023: Period Total Number of Shares Purchased (1) Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number (or Approximate Dollar Value) of Shares That May Yet Be Purchased Under the Plans or Programs October 1, 2023 through October 31, 2023 47,887 $ 10.46 — — November 1, 2023 through November 30, 2023 12,420 $ 10.66 — — December 1, 2023 through December 31, 2023 38,804 $ 13.61 — — Total 99,111 $ 11.72 — — ______________________________ (1) Represents shares of common stock withheld to satisfy taxes associated with the vesting of restricted stock awards.
Biggest changeIssuer Purchases of Equity Securities The following table provides certain information with respect to purchase of our common stock during the three months ended December 31, 2024: Period Total Number of Shares Purchased (1) Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number (or Approximate Dollar Value) of Shares That May Yet Be Purchased Under the Plans or Programs October 1, 2024 through October 31, 2024 39,319 $ 10.38 — — November 1, 2024 through November 30, 2024 20,565 $ 10.62 — — December 1, 2024 through December 31, 2024 20,447 $ 9.36 — — Total 80,331 $ 10.18 — — ______________________________ (1) Represents shares of common stock withheld to satisfy taxes associated with the vesting of restricted stock awards.
We currently intend to retain any future earnings to finance the development and growth of our business. We do not intend to declare or pay cash dividends to our stockholders in the foreseeable future. Recent Sales of Unregistered Securities None.
We currently intend to retain any future earnings to finance the development and growth of our business. We do not intend to declare or pay cash dividends to our stockholders in the foreseeable future.
The closing price for our common stock as reported by the NASDAQ Global Market on February 13, 2024 was $12.80 per share. As of February 13, 2024, there were 17 holders of record of our common stock. Dividends We have never declared or paid any dividends on our capital stock.
The closing price for our common stock as reported by the NASDAQ Global Market on February 10, 2025 was $9.64 per share. As of February 10, 2025, there were 14 holders of record of our common stock. Dividends We have never declared or paid any dividends on our capital stock.
Pursuant to applicable SEC rules, all values assume reinvestment of the full amount of all dividends, however no dividends have been declared on our common stock to date.
The graph shows the value at the end of each of the last five fiscal years of $100 invested in our common stock. Pursuant to applicable SEC rules, all values assume reinvestment of the full amount of all dividends, however no dividends have been declared on our common stock to date.
Performance Graph The following performance graph compares the cumulative total return on our common stock during the last five fiscal years with the NASDAQ Composite Index (U.S.) and the NASDAQ Biotechnology Index during the same period. The graph shows the value at the end of each of the last five fiscal years, of $100 invested in our common stock.
Recent Sales of Unregistered Securities None. -70- Table of Contents Performance Graph The following performance graph compares the cumulative total return on our common stock during the last five fiscal years with the NASDAQ Composite Index (U.S.) and the NASDAQ Biotechnology Index during the same period.
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The stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Amicus Therapeutics, Inc. $100 $237 $119 $122 $146 $97 NASDAQ Composite $100 $144 $174 $116 $165 $215 NASDAQ Biotechnology $100 $126 $125 $110 $118 $114 The stock price performance included in this graph is not necessarily indicative of future stock price performance.

Item 7. Management's Discussion & Analysis

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

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Biggest changeIn October 2023, the Company voluntarily prepaid the outstanding principal amount, accrued interest and prepayment premiums of the Senior Secured Term Loan due 2026. As a result of this early extinguishment, a loss on extinguishment of debt of $13.9 million was recognized in the Consolidated Statements of Operations. Interest Expense.
Biggest changeRestructuring charges were primarily related to an initiative to reduce operating costs by abandoning a lease that we no longer believe is useful in our operations. Loss on extinguishment of debt. In October 2023, the Company voluntarily prepaid the outstanding principal amount, accrued interest and prepayment premiums of the Senior Secured Term Loan due 2026.
Our two marketed therapies are Galafold ® , the first oral monotherapy for people living with Fabry disease who have amenable genetic variants, and Pombiliti ™ + Opfolda ™ , a novel treatment designed to improve uptake of active enzyme into key disease relevant tissues for adults living with late-onset Pompe disease.
Our two marketed therapies are Galafold ® , the first oral monotherapy for people living with Fabry disease who have amenable genetic variants, and Pombiliti ® + Opfolda ® , a novel two-component treatment designed to improve uptake of active enzyme into key disease relevant tissues for adults living with late-onset Pompe disease.
The net cash used in operations was also impacted by an increase in accounts payable and accrued expenses of $49.2 million, associated with accrued interest due to timing, inventory purchases to support our continued commercial growth, personnel costs, and an increases in sales rebates associated with increased commercial sales.
The net cash used in operations was also impacted by an increase in accounts payable and accrued expenses of $49.2 million, associated with accrued interest due to timing, inventory purchases to support our continued commercial growth, personnel costs, and an increase in sales rebates associated with increased commercial sales.
Our future capital requirements will depend on a number of factors, including: • the scope, progress, results and costs of clinical trials for our drug candidates; • the cost of manufacturing drug supply for our commercial, clinical and preclinical studies, including the cost of manufacturing Pombiliti ™ (also referred to as "ATB200" or "cipaglucosidase alfa"); • the future results of preclinical research and subsequent clinical trials for pipeline candidates we may identify from time to time, including our ability to obtain regulatory approvals and commercialize such therapies; • the costs, timing, and outcome of regulatory review of our product candidates; • any changes in regulatory standards relating to the review of our product candidates; • any changes in laws, rules or regulations affecting our ability to manufacture, transport, test, develop, or commercialize our products, including Galafold ® , Pombiliti ™ + Opfolda ™ , or our product candidates; • the costs of commercialization activities, including product marketing, sales, and distribution; • the emergence of competing technologies and other adverse market developments; • the estimates regarding the potential market opportunity for our products and product candidates; • our ability to successfully commercialize Galafold ® (also referred to as "migalastat HCl"); • our ability to successfully commercialize Pombiliti ™ + Opfolda ™ (together, also referred to as "AT-GAA") in the E.U., U.K., and U.S., and elsewhere, if regulatory applications are approved; • our ability to manufacture or supply sufficient clinical or commercial products, including Galafold ® and Pombiliti ™ + Opfolda ™ ; • our ability to obtain reimbursement for Galafold ® and Pombiliti ™ + Opfolda ™ ; -77- Table of Contents • our ability to satisfy post-marketing commitments or requirements for continued regulatory approval of Galafold ® and Pombiliti ™ + Opfolda ™ ; • our ability to obtain market acceptance of Galafold ® and Pombiliti ™ + Opfolda ™ or any other product developed or acquired that has received regulatory approval; • the costs of preparing, filing, and prosecuting patent applications and maintaining, enforcing, and defending intellectual property-related claims, including Hatch-Waxman litigation; • the impact of litigation that has been or may be brought against us or of litigation that we are pursuing or may pursue against others, including Hatch-Waxman litigation; • the extent to which we acquire or invest in businesses, products, and technologies; • our ability to successfully integrate acquired products and technologies into our business, or successfully divest or license existing products and technologies from our business, including the possibility that the expected benefits of the transactions will not be fully realized by us or may take longer to realize than expected; • our ability to establish licensing agreements, collaborations, partnerships or other similar arrangements and to obtain milestone, royalty, or other economic benefits from any such collaborators; • the costs associated with, and our ability to comply with, emerging environmental, social and governance standards, including climate reporting requirements at the local, state and national levels; • our ability to successfully protect our information technology systems and maintain our global operations and supply chain without interruption; • our ability to accurately forecast revenue, operating expenditures, or other metrics impacting profitability; • fluctuations in foreign currency exchange rates; and • changes in accounting standards.
Our future capital requirements will depend on a number of factors, including: • the scope, progress, results and costs of clinical trials for our drug candidates; • the cost of manufacturing drug supply for our commercial, clinical and preclinical studies, including the cost of manufacturing Pombiliti ® (also referred to as "ATB200" or "cipaglucosidase alfa"); • the future results of preclinical research and subsequent clinical trials for pipeline candidates we may identify from time to time, including our ability to obtain regulatory approvals and commercialize such therapies; • the costs, timing, and outcome of regulatory review of our product candidates; • any changes in regulatory standards relating to the review of our product candidates; • any changes in laws, rules or regulations affecting our ability to manufacture, transport, test, develop, or commercialize our products, including Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates; • the costs of commercialization activities, including product marketing, sales, and distribution; • the emergence of competing technologies and other adverse market developments; • the estimates regarding the potential market opportunity for our products and product candidates; • our ability to successfully commercialize Galafold ® (also referred to as "migalastat HCl"); • our ability to successfully commercialize Pombiliti ® + Opfolda ® (together, also referred to as "AT-GAA") in the E.U., U.K., and U.S., and elsewhere, if regulatory applications are approved; • our ability to manufacture or supply sufficient clinical or commercial products, including Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain reimbursement for Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to satisfy post-marketing commitments or requirements for continued regulatory approval of Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain market acceptance of Galafold ® and Pombiliti ® + Opfolda ® or any other product developed or acquired that has received regulatory approval; • the costs of preparing, filing, and prosecuting patent applications and maintaining, enforcing, and defending intellectual property-related claims, including Hatch-Waxman litigation; • the impact of litigation that has been or may be brought against us or of litigation that we are pursuing or may pursue against others, including Hatch-Waxman litigation; • the extent to which we acquire or invest in businesses, products, and technologies; • our ability to successfully integrate acquired products and technologies into our business, or successfully divest or license existing products and technologies from our business, including the possibility that the expected benefits of the transactions will not be fully realized by us or may take longer to realize than expected; • our ability to establish licensing agreements, collaborations, partnerships or other similar arrangements and to obtain milestone, royalty, or other economic benefits from any such collaborators; • the costs associated with, and our ability to comply with, emerging sustainability standards, including climate reporting requirements at the local, state and national levels, especially abroad; • our ability to successfully protect our information technology systems and maintain our global operations and supply chain without interruption; • our ability to accurately forecast revenue, operating expenditures, or other metrics impacting profitability; • fluctuations in foreign currency exchange rates; and -77- Table of Contents • changes in accounting standards.
We have historically funded our operations through stock offerings, product revenues, debt issuance, collaborations, and other financing arrangements. Sources of Liquidity In November 2022, we entered into a Sales Agreement with The Goldman Sachs & Co.
We have historically funded our operations through stock offerings, product revenues, debt issuance, collaborations, and other financing arrangements. Sources of Liquidity In November 2022, we entered into a Sales Agreement with Goldman Sachs & Co.
The change in operating assets was primarily due to an increase in inventory of $44.6 million, an increase in accounts receivable of $20.1 million associated with increased commercial sales, and an increase in prepaid and other current assets of $8.1 million primarily associated with tax prepayments.
The change in operating assets was primarily due to increases in inventory of $44.6 million, an increase in accounts receivable of $20.1 million associated with increased commercial sales, and an increase in prepaid and other current assets of $8.1 million primarily associated with tax prepayments.
Discussions of 2021 items and year-to-year comparisons between 2022 and 2021 that are not included in this Form 10-K can be found in Part II, Item 7 of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, which comparisons are hereby incorporated by reference.
Discussions of 2022 items and year-to-year comparisons between 2023 and 2022 that are not included in this Form 10-K can be found in Part II, Item 7 of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, which comparisons are hereby incorporated by reference.
As of December 31, 2023, an aggregate of $184.4 million worth of shares remain available to be issued and sold under the ATM program. In October 2023, we entered into the Senior Secured Term Loan due 2029. This transaction resulted in net proceeds of $387.4 million, after deducting fees and expenses.
As of December 31, 2024, an aggregate of $164.2 million worth of shares remain available to be issued and sold under the ATM program. In October 2023, we entered into the Senior Secured Term Loan due 2029. This transaction resulted in net proceeds of $387.4 million, after deducting fees and expenses.
As of December 31, 2023, remaining milestones under this agreement were $9.8 million. Refer to "— Note 14. Collaborative Agreements," to the Consolidated Financial Statements for more information. We have a number of binding minimum purchase and manufacturing commitments due to our third-party manufacturers.
As of December 31, 2024, remaining milestones under this agreement were $8.5 million. Refer to "— Note 14. Collaborative Agreements," to the Consolidated Financial Statements for more information. We have a number of binding minimum purchase and manufacturing commitments due to our third-party manufacturers.
Net Cash Provided by (Used in) Financing Activities Net cash provided by financing activities for the year ended December 31, 2023 was $61.7 million.
Net cash provided by financing activities for the year ended December 31, 2023 was $61.7 million.
Net Cash Used in Operating Activities Net cash used in operations for the year ended December 31, 2023 was $69.1 million.
Net cash used in operations for the year ended December 31, 2023 was $69.1 million.
These purchase obligations are in addition to amounts recorded on our December 31, 2023 Consolidated Balance Sheets. We have no off-balance sheet arrangements as of December 31, 2023 and 2022. -78- Table of Contents Recent Accounting Pronouncements Please refer to "— Note 2. Summary of Significant Accounting Policies," in our Notes to the Consolidated Financial Statements.
These purchase obligations are in addition to amounts recorded on our December 31, 2024 Consolidated Balance Sheets. We have no off-balance sheet arrangements as of December 31, 2024 and 2023. Recent Accounting Pronouncements Please refer to "— Note 2. Summary of Significant Accounting Policies," in our Notes to the Consolidated Financial Statements.
Potential impacts of business development collaborations, pipeline expansion, and investment in manufacturing capabilities could impact our long-term capital requirements. Contractual Obligations and Commitments As of December 31, 2023, remaining maturities, including expected interest payments through maturity, on our Senior Secured Term Loan due 2029 were $623.4 million. Refer to "— Note 11.
Potential impacts of business development collaborations, pipeline expansion, and investment in manufacturing capabilities could impact our long-term capital requirements. Contractual Obligations and Commitments As of December 31, 2024, remaining maturities, including expected interest payments through maturity, on our Senior Secured Term Loan due 2029 were $548.3 million. Refer to "— Note 11.
Debt," to the Consolidated Financial Statements for more information. We are lessees to various operating leases for facilities and equipment. As of December 31, 2023, our undiscounted cash liabilities for operating leases were $89.8 million, with maturities ranging up through fiscal 2034. Refer to “— Note 12. Leases,” to the Consolidated Financial Statements for more information.
Debt," to the Consolidated Financial Statements for more information. We are lessees to various operating leases for facilities and equipment. As of December 31, 2024, our undiscounted cash liabilities for operating leases were $81.0 million, with maturities ranging up through fiscal 2034. Refer to “— Note 12. Leases,” to the Consolidated Financial Statements for more information.
The following section generally discusses 2023 and 2022 items and year-to-year comparisons between 2023 and 2022.
The following section generally discusses 2024 and 2023 items and year-to-year comparisons between 2024 and 2023.
Additionally, Pombiliti ™ + Opfolda ™ has been granted orphan drug designation in the U.S., E.U., U.K., Japan and several other countries. -72- Table of Contents Consolidated Results of Operations The following discussion should be read in conjunction with the Consolidated Financial Statements and related notes included elsewhere in this report.
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U. -72- Table of Contents Consolidated Results of Operations The following discussion should be read in conjunction with the Consolidated Financial Statements and related notes included elsewhere in this report.
Our tax liabilities are largely dependent on the distributions of pre-tax earnings among the many jurisdictions in which we operate. -74- Table of Contents Critical Accounting Policies and Significant Judgments and Estimates The discussion and analysis of our financial condition and results of operations are based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles ("U.S.
Our tax liabilities are largely dependent on the mix of pre-tax earnings among the many jurisdictions in which we operate and differences in the timing of the recognition of such earnings under the relevant accounting standards and tax rules. -74- Table of Contents Critical Accounting Policies and Significant Judgments and Estimates The discussion and analysis of our financial condition and results of operations are based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles ("U.S.
Pombiliti ™ + Opfolda ™ (also referred to as "cipaglucosidase alfa-atga/miglustat") was approved in 2023 in the three largest Pompe markets: the U.S., the E.U., and the U.K. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., and Switzerland. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Net cash provided by investing activities for the year ended December 31, 2022 was $92.3 million. Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures.
Net Cash Used in (Provided by) Investing Activities Net cash used in investing activities for the year ended December 31, 2024 was $0.6 million. Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures.
As of December 31, 2023, these purchase and manufacturing obligations totaled $126.2 million, of which $83.9 million and $42.3 million are expected in 2024 and 2025, respectively. Contracts for which our commitment is variable, based on volumes, with no fixed minimum quantities, and contracts that can be canceled without payment penalties have been excluded.
As of December 31, 2024, these purchase and manufacturing obligations totaled $179.7 million, of which $102.7 million and $77.0 million are expected in 2025 and 2026, respectively. Contracts for which our commitment is variable, based on volumes, with no fixed minimum quantities, and contracts that can be canceled without payment penalties have been excluded.
Net product sales increased $70.1 million during the year ended December 31, 2023 compared to the prior year. The increase was primarily due to continued growth of Galafold ® in the U.S., Europe, and Japan markets as well as our commercial launch of Pombiliti ™ + Opfolda ™ in Europe and the U.S. Cost of goods sold .
Net product sales increased $128.9 million during the year ended December 31, 2024 compared to the prior year. The increase was primarily due to both the continued growth of Galafold ® in Europe and the U.S. as well as the launch of Pombiliti ® + Opfolda ® in Europe and the U.S. Cost of goods sold .
The income tax expense for the year ended December 31, 2023 was $1.5 million. We are subject to income taxes in various jurisdictions.
The income tax expense for the year ended December 31, 2024 was $27.4 million. We are subject to income taxes in various jurisdictions.
During the year ended December 31, 2023, we issued and sold an aggregate of 5,244,936 shares through our ATM program at a weighted-average public offering price of $12.50 per share, resulting in net proceeds of $63.1 million.
During the year ended December 31, 2024, we issued and sold an aggregate of 1,732,204 shares through our ATM program at a weighted-average public offering price of $11.69 per share, resulting in net proceeds of $19.6 million.
The components of net cash used in operations included the net loss for the year ended December 31, 2022 of $236.6 million and the net change in operating assets and liabilities of $39.9 million offset by $76.5 million of stock compensation and $33.4 million of other non-cash adjustments.
The components of net cash used in operations included the net loss for the year ended December 31, 2024 of $56.1 million and the net change in operating assets and liabilities of $98.9 million partially offset by $84.9 million of stock compensation and $36.3 million of other non-cash adjustments.
Net cash used in operations for the year ended December 31, 2022 was $166.6 million.
Net Cash Used in Operating Activities Net cash used in operations for the year ended December 31, 2024 was $33.9 million.
Cost of goods sold includes manufacturing costs for our commercial products as well as royalties associated with net product sales of Galafold ® . Cost of goods sold as a percentage of net product sales decreased 2.4% primarily due to inventory write-offs in the prior year.
Cost of goods sold includes manufacturing costs for our commercial products as well as royalties associated with net product sales of Galafold ® . Cost of goods sold as a percentage of net product sales increased 0.7% primarily due to inventory write-offs associated with validation efforts during the first quarter of 2024. -73- Table of Contents Research and Development Expense.
Net cash provided by financing activities was partially offset by the $408.0 million repayment of our Senior Secured Loan due in 2026, and $17.9 million for payments of employee withholding taxes related to restricted stock unit vesting. Net cash used in financing activities for the year ended December 31, 2022 was $7.5 million.
Net cash provided by financing activities was partially offset by the $408.0 million repayment of our Senior Secured Loan due in 2026, and $17.9 million for payments of employee withholding taxes related to restricted stock unit vesting. -76- Table of Contents Funding Requirements We expect to continue to incur significant costs in the foreseeable future primarily due to research and development expenses, including expenses related to conducting clinical trials.
Net cash used in financing activities primarily reflects $11.5 million from payments of employee withholding taxes related to restricted stock unit vesting, partially offset by $4.3 million from the exercise of stock options.
Net cash provided by financing activities primarily reflects $19.6 million of net proceeds from the issuance of shares in connection with our ATM program and $7.7 million in proceeds from the exercise of stock options, partially offset by $22.0 million for payments of employee withholding taxes related to restricted stock unit vesting.
Year Ended December 31, 2023 Compared to Year Ended December 31, 2022 The following table provides selected financial information of our operations: Years Ended December 31, (in thousands) 2023 2022 Change Net product sales $ 399,356 $ 329,233 $ 70,123 Cost of goods sold 37,326 38,599 (1,273) Cost of goods sold as a percentage of net product sales 9.3 % 11.7 % (2.4) % Operating expenses: Research and development 152,381 276,677 (124,296) Selling, general, and administrative 275,270 213,041 62,229 Changes in fair value of contingent consideration payable 2,583 1,078 1,505 Loss on impairment of assets 1,134 6,616 (5,482) Depreciation and amortization 7,873 5,342 2,531 Other (expense) income: Interest income 7,078 3,024 4,054 Interest expense (50,149) (37,119) (13,030) Loss on extinguishment of debt (13,933) — (13,933) Other (expense) income (15,886) 4,176 (20,062) Income tax (expense) benefit (1,483) 5,471 (6,954) Net loss attributable to common stockholders $ (151,584) $ (236,568) $ 84,984 Net Product Sales.
Year Ended December 31, 2024 Compared to Year Ended December 31, 2023 The following table provides selected financial information of our operations: Years ended December 31, (in thousands) 2024 2023 Change Net product sales $ 528,295 $ 399,356 $ 128,939 Cost of goods sold 52,943 37,326 15,617 Cost of goods sold as a percentage of net product sales 10.0 % 9.3 % 0.7 % Operating expenses: Research and development 109,362 152,381 (43,019) Selling, general, and administrative 323,379 275,270 48,109 Changes in fair value of contingent consideration payable — 2,583 (2,583) Loss on impairment of assets — 1,134 (1,134) Restructuring charges 9,188 — 9,188 Depreciation and amortization 8,547 7,873 674 Other (expense) income: Interest income 5,407 7,078 (1,671) Interest expense (49,598) (50,149) 551 Loss on extinguishment of debt — (13,933) 13,933 Other expense (9,441) (15,886) 6,445 Income tax expense (27,350) (1,483) (25,867) Net loss attributable to common stockholders $ (56,106) $ (151,584) $ 95,478 Net Product Sales.
The following table summarizes our principal product development programs for each product candidate in development, and the out-of-pocket, third-party expenses incurred with respect to each product candidate: (in thousands) Years Ended December 31, Projects 2023 2022 Third-party direct project expenses Galafold ® (Fabry Disease) $ 12,928 $ 15,012 Pombiliti ™ + Opfolda ™ (Pompe Disease) 58,826 99,584 Gene therapy programs 872 48,948 Pre-clinical and other programs 1,681 124 Total third-party direct project expenses 74,307 163,668 Other project costs 1 Personnel costs 62,492 82,386 Other costs 15,582 30,623 Total other project costs 78,074 113,009 Total research and development costs $ 152,381 $ 276,677 The $124.3 million decrease in research and development costs was primarily driven by the strategic deprioritization of our gene therapy portfolio, which resulted in the recognition of contract exit costs in the prior year.
The following table summarizes our principal product development programs for each product candidate in development, and the out-of-pocket, third-party expenses incurred with respect to each product candidate: (in thousands) Years ended December 31, Projects 2024 2023 Third-party direct project expenses Galafold ® (Fabry Disease) $ 9,298 $ 12,928 Pombiliti ® + Opfolda ® (Pompe Disease) 45,215 58,826 Pre-clinical and other programs 2,437 2,553 Total third-party direct project expenses 56,950 74,307 Other project costs 1 Personnel costs 41,405 62,492 Other costs 11,007 15,582 Total other project costs 52,412 78,074 Total research and development costs $ 109,362 $ 152,381 The $43.0 million decrease in research and development costs was primarily driven by our Pombiliti ® + Opfolda ® commercial launch, decreasing both clinical spend and the number of employees supporting research and development efforts.
Net cash provided by investing activities reflects $335.9 million for the sale and redemption of marketable securities and $3.4 million of proceeds from the sale of our property and equipment, partially offset by $243.3 million for the purchase of marketable securities and $3.8 million for capital expenditures.
Net cash used in investing activities reflects $114.8 million for the purchase of marketable securities and $3.6 million for capital expenditures, partially offset by $117.8 million for the sale and redemption of marketable securities. Net cash provided by investing activities for the year ended December 31, 2023 was $98.1 million.
Interest expense increased $13.0 million during the year ended December 31, 2023. The increase was due to a higher variable interest rate on debt year over year. Other (Expense) Income . The $20.1 million variance was primarily related to movement in foreign exchange rates caused by remeasurement of foreign-denominated balances. Income Tax Expense.
As a result of this early extinguishment, a loss on extinguishment of debt of $13.9 million was recognized in the Consolidated Statements of Operations. Other (Expense) Income . The $6.4 million variance was primarily related to the movement in foreign exchange rates caused by remeasurement of foreign-denominated balances. Income Tax Expense.
Selling, general, and administrative expense increased $62.2 million, primarily driven by personnel costs in connection with the reallocation of resources to support our Pombiliti ™ + Opfolda ™ commercial launch and third-party professional fees. Loss on Impairment of Assets.
Selling, General, and Administrative Expense. Selling, general, and administrative expense increased $48.1 million, primarily driven by personnel costs resulting from an increase in the number of employees to support our commercial launch activities, external costs required to support the manufacture and sale of our commercial products, and third-party professional fees. Restructuring Charges.
The change in operating assets was primarily due to increases in accounts receivable of $17.3 million due to increased commercial sales of Galafold ® , an increase in prepaid and other current assets of $6.2 million to support commercial activities for Galafold ® , and an increase in inventory of $5.3 million.
The change in operating assets was primarily due to an increase in inventory of $73.7 million to support our continued commercial growth, an increase in accounts receivable of $19.5 million, and a decrease in accounts payable and accrued expenses of $16.5 million associated with timing of payments, partially offset by an decrease in prepaid expenses and other current assets by $14.0 million.
We used proceeds from the Senior Secured Term Loan due 2029 and the private placement to prepay the Senior Secured Term Loan due 2026, inclusive of the outstanding principal amount, accrued interest and prepayment premium. -75- Table of Contents In September 2021, we entered into securities purchase agreements with certain investors for the private placement of an aggregate of 11,296,660 shares of our common stock, at a purchase price of $10.18 per share, and pre-funded warrants to purchase an aggregate of 8,349,705 shares of common stock, at a purchase price of $10.17 per pre-funded warrant.
We used proceeds from the Senior Secured Term Loan due 2029 and the private placement to prepay the Senior Secured Term Loan due 2026, inclusive of the outstanding principal amount, accrued interest and prepayment premium. -75- Table of Contents Cash Flow Discussion As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $249.9 million.
Removed
A portion of inventory available for sale was expensed as research and development costs prior to regulatory approval and as such, the cost of goods sold and related gross margins are not necessarily indicative of future costs of goods sold and gross margin. -73- Table of Contents Research and Development Expense.
Added
Net Cash Provided by Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 was $5.1 million.
Removed
Additionally, Pompe disease program spend decreased due to reduced clinical manufacturing costs. Personnel and other costs decreased in connection with the reallocation of resources to support our Pombiliti ™ + Opfolda ™ commercial launch and continued growth of Galafold ® . Selling, General, and Administrative Expense.
Removed
The $5.5 million decrease was primarily in connection with the strategic deprioritization of our gene therapy portfolio in the prior year, which resulted in us recognizing a loss on impairment of assets. Loss on Extinguishment of Debt .
Removed
The net proceeds from these private placements were approximately $199.8 million. Cash Flow Discussion As of December 31, 2023, we had cash, cash equivalents, and marketable securities of $286.2 million.
Removed
The net cash used in operations was also impacted by a decrease in accounts payable and accrued expenses of $6.4 million, associated with payments of contract manufacturing and third-party development services partially offset by increases in sales rebates and royalties associated with increased commercial sales of Galafold ® . -76- Table of Contents Net Cash Provided by Investing Activities Net cash provided by investing activities for the year ended December 31, 2023 was $98.1 million.
Removed
Funding Requirements We expect to continue to incur significant costs in the foreseeable future primarily due to research and development expenses, including expenses related to conducting clinical trials.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

4 edited+2 added−1 removed5 unchanged
Biggest changeThe annual average variable interest rate for our variable rate debts during the year ended December 31, 2023 was 11.7%. A hypothetical 100 basis point increase or decrease in the average interest rate on our variable rate debts would result in $4.1 million change in the interest expense as of December 31, 2023.
Biggest changeA hypothetical 100 basis point increase or decrease in the average interest rate on our variable rate debts would result in $4.1 million change in the interest expense as of December 31, 2024. -78- Table of Contents We face foreign exchange risk as a result of entering into transactions denominated in currencies other than U.S. dollars, primarily in British pounds ("GBP").
At December 31, 2023, we had a $400 million Senior Secured Term Loan due 2029 that bears interest at a rate equal to the 3-month Term Secured Overnight Financing Rate ("SOFR"), subject to a 2.5% floor, plus a Term SOFR adjustment of 0.26161% and a margin of 6.25% per year.
At December 31, 2024, we had a $400 million Senior Secured Term Loan due 2029 that bears interest at a rate equal to the 3-month Term Secured Overnight Financing Rate ("SOFR"), subject to a 2.5% floor, plus a Term SOFR adjustment of 0.26161% and a margin of 6.25% per year.
The securities in our investment portfolio are not leveraged, are classified as available-for-sale and, due to the short-term nature, are subject to minimal interest rate risk. We believe that a 1% (100 basis points) change in average interest rates would either increase or decrease the market value of our investment portfolio by $0.1 million as of December 31, 2023.
The securities in our investment portfolio are not leveraged, are classified as available-for-sale and, due to the short-term nature, are subject to minimal interest rate risk. We believe that a 1% (100 basis points) change in average interest rates would either increase or decrease the market value of our investment portfolio by $0.4 million as of December 31, 2024.
We face foreign exchange risk as a result of entering into transactions denominated in currencies other than U.S. dollars. We are not currently engaged in any foreign currency hedging activities. The current exposures arise primarily from cash, accounts receivable, intercompany receivables and payables, and net product sales denominated in foreign currencies.
We are not currently engaged in any foreign currency hedging activities. The current exposures arise primarily from cash, accounts receivable, intercompany receivables and payables, and net product sales denominated in foreign currencies.
Removed
A hypothetical 10% change in foreign exchange rates during any of the periods presented would not have had a material impact on our Consolidated Financial Statements. -79- Table of Contents
Added
The annual average variable interest rate for our variable rate debts during the year ended December 31, 2024 was 11.7%.
Added
Based on our foreign currency denominated exposures as of December 31, 2024, we believe that a near-term 10% fluctuation of the USD to GBP exchange rate could result in a potential change in the fair value of our net GBP denominated assets and liabilities of approximately $57.4 million. -79- Table of Contents

Other FOLD 10-K year-over-year comparisons