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What changed in BIOMARIN PHARMACEUTICAL INC's 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of BIOMARIN PHARMACEUTICAL INC's 2024 and 2025 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 2025 report.

+520 added−417 removedSource: 10-K (2026-02-26) vs 10-K (2025-02-24)

Top changes in BIOMARIN PHARMACEUTICAL INC's 2025 10-K

520 paragraphs added · 417 removed · 329 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

111 edited+48 added−43 removed211 unchanged
Biggest changeGeneral Subject Matter Patent Expiration BRINEURA U.S. 9,044,473 Method of treatment by administration into the cerebrospinal fluid February 18, 2031 10,279,015 Formulation; kit May 5, 2036 EU EP3294345 Formulation May 5, 2036 PALYNZIQ U.S. 7,534,595 Composition; method of treating May 24, 2032 (1) 10,221,408 Purification February 3, 2031 9,557,340 Antibody detection assay July 30, 2029 11,505,790 Regimen February 3, 2031 11,919,633 Method of treating adolescent subjects May 18, 2042 EU 2152868 Composition; pharmaceutical composition May 23, 2028 / May 23, 2033 (2) 2531209; 3025728 Formulation; purification February 3, 2031 ROCTAVIAN US 9,504,762; 10,463,718; 11,406,690 Compositions, Methods of Treatment, Production September 10, 2034 (3) 10,512,675; 11,690,898 Formulation, Clinical Methods of Treatment April 10, 2037 December 19, 2038 EU 3044231 Compositions, Methods of Treatment September 10, 2034 (4) VIMIZIM U.S. 8,128,925 Compositions; methods of treatment April 10, 2030 8,765,437 Purification; formulation; methods of treatment January 10, 2032 EU 2245145 Composition; use for treating April 30, 2029 (5) 2595650 Purification; composition; use for treating; formulation July 22, 2031 3219795 Method of producing January 16, 2029 VOXZOGO U.S. 8,198,242 Compositions, Methods of Treatment June 11, 2030 (6) 9,907,834 Formulation August 1, 2036 10,646,550 Clinical methods of treatment August 1, 2036 EU 2432489 Compositions, Methods of Treatment May 20, 2030 (7) 3328416 Formulation, Use August 1, 2036 (1) Date of expiry includes the granted patent term extension (PTE).
Biggest changeGeneral Subject Matter Patent Expiration BRINEURA U.S. 10,279,015 Formulation; kit May 5, 2036 EU EP3294345 Formulation May 5, 2036 PALYNZIQ U.S. 7,534,595 Composition; method of treating May 24, 2032 (1) 10,221,408 Purification February 3, 2031 9,557,340 Antibody detection assay July 30, 2029 11,505,790 Regimen February 3, 2031 11,918,633 Method of treating adolescent subjects May 18, 2042 EU 2152868 Composition; pharmaceutical composition May 23, 2028 / May 23, 2033 (2) 2531209; 3025728 Formulation; purification February 3, 2031 VIMIZIM U.S. 8,128,925 Compositions; methods of treatment January 16, 2029 8,765,437 Purification; formulation; methods of treatment January 10, 2032 EU 2245145 Composition; use for treating April 30, 2029 (3) 2595650 Purification; composition; use for treating; formulation July 22, 2031 3219795 Method of producing January 16, 2029 VOXZOGO U.S. 8,198,242 Compositions, Methods of Treatment June 11, 2030 (4) 9,907,834 Formulation August 1, 2036 10,646,550 Clinical methods of treatment August 1, 2036 EU 2432489 Compositions, Methods of Treatment May 20, 2030 (5) 3328416 Formulation, Use August 1, 2036 (1) For PALYNZIQ, the date of expiry includes the granted patent term extension (PTE).
In the EU, a MA may be granted to a similar medicinal product with the same orphan indication during the regulatory exclusivity period with the consent of the MA holder for the original orphan medicinal product or if the MA holder of the original orphan medicinal product is unable to supply sufficient quantities.
In the EU, a MA may be granted to a similar medicinal product with the same orphan indication during the regulatory exclusivity period with the consent of the MA holder for the original orphan medicinal product or if the MA holder of the original orphan medicinal product is unable to supply sufficient quantities of the orphan product.
The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product is eligible for exclusivity precluding marketing of interchangeable biosimilars referencing the same reference product for the lesser of (i) one year after first commercial marketing of the first interchangeable biosimilar to be approved, (ii) eighteen months after the first interchangeable biosimilar is approved if there is not patent challenge, (iii) eighteen months after resolution of a lawsuit over the patents of the reference biologic in favor of the first interchangeable biosimilar applicant, or (iv) 42 months after the first interchangeable biosimilar’s application has been approved if the interchangeable applicant has been sued under the BPCIA and any related patent litigation is ongoing within the 42-month period.
The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product is eligible for exclusivity precluding marketing of other interchangeable biosimilars referencing the same reference product for the lesser of (i) one year after first commercial marketing of the first interchangeable biosimilar to be approved, (ii) eighteen months after the first interchangeable biosimilar is approved if there is not patent challenge, (iii) eighteen months after resolution of a lawsuit over the patents of the reference biologic in favor of the first interchangeable biosimilar applicant, or (iv) 42 months after the first interchangeable biosimilar’s application has been approved if the interchangeable applicant has been sued under the BPCIA and any related patent litigation is ongoing within the 42-month period.
These symptoms include: inhibited growth, spinal cord compression, enlarged liver and spleen, joint deformities and reduced range of motion, skeletal deformities, impaired cardiovascular function, upper airway obstruction, reduced pulmonary function, frequent ear and lung infections, impaired hearing and vision, sleep apnea, malaise and reduced endurance. NAGLAZYME is approved for marketing in the U.S., the EU and other international markets.
These symptoms include: inhibited growth, spinal cord compression, enlarged liver and spleen, joint deformities and reduced range of motion, skeletal deformities, impaired cardiovascular function, upper airway obstruction, reduced pulmonary function, frequent ear and lung infections, impaired hearing and vision, sleep apnea, malaise and reduced endurance. 6 NAGLAZYME is approved for marketing in the U.S., the EU and other international markets.
This excludes so-called clock stops, during which additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP. At the end of the review period, the CHMP provides an opinion to the EC. If the opinion is favorable, the EC may then adopt a decision to grant marketing authorization.
However, this excludes so-called clock stops, during which additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP. At the end of the review period, the CHMP provides an opinion to the EC. If the opinion is favorable, the EC may then adopt a decision to grant marketing authorization.
The overall ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. 18 Orphan Drug Designation Orphan drug designation is granted by the FDA and the EC to drugs intended to treat a rare disease or condition, which in the U.S. is defined as having a prevalence of less than 200,000 individuals in the U.S. or as a condition that affects more than 200,000 individuals in the U.S. and for which there is no reasonable expectation that the costs of development of said drug will be recovered from sales in the U.S.
The overall ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. 19 Orphan Drug Designation Orphan drug designation is granted by the FDA and the EC to drugs intended to treat a rare disease or condition, which in the U.S. is defined as having a prevalence of less than 200,000 individuals in the U.S. or as a condition that affects more than 200,000 individuals in the U.S. and for which there is no reasonable expectation that the costs of development of said drug will be recovered from sales in the U.S.
Once all the studies and measures agreed have been conducted in accordance with the PIP, products are eligible for a six -month extension of the protection under a supplementary protection certificate (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two -year extension of the orphan market exclusivity.
Currently, once all the studies and measures agreed have been conducted in accordance with the PIP, products are eligible for a six -month extension of the protection under a supplementary protection certificate (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two -year extension of the orphan market exclusivity.
Based on these rules, a body of industry guidelines and sometimes national laws in force in individual EU Member States has been introduced to fight improper payments or other transfers of value to HCPs, and in general inducements that may have a broadly promotional character.
Based on these rules, a body of industry guidelines and sometimes national laws in force in individual EU Member States 21 has been introduced to fight improper payments or other transfers of value to HCPs, and in general inducements that may have a broadly promotional character.
The FDA may also refer applications for novel products or products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved.
The FDA may also refer applications for novel products or products that present difficult questions of 15 safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved.
The IRA also requires manufacturers to provide annual Medicare Part D rebates for single-source drugs and biological products with prices that increase faster than the rate of inflation, and in November 2024, CMS finalized regulations pertaining to Medicare Part D inflation rebates. The IRA also allows the U.S.
The IRA also requires manufacturers to provide annual Medicare Part D rebates for single-source drugs and biological products with prices that increase faster than the rate of inflation, and in November 2024, CMS finalized regulations pertaining to Medicare Part D inflation rebates. The IRA also requires the U.S.
For the FDA, the review period for standard review applications for new molecular 14 entities is typically ten months from the date the company files the application and, for priority review of drugs, that is, drugs that the FDA determines address a significant unmet need and represent a significant improvement over existing therapy, the review period is typically six months from the date the company files the application.
For the FDA, the review period for standard review applications for new molecular entities is typically ten months from the date the company files the application and, for priority review of drugs, that is, drugs that the FDA determines address a significant unmet need and represent a significant improvement over existing therapy, the review period is typically six months from the date the company files the application.
Their products may outcompete ours due to one or more factors, including faster progress through preclinical 9 and clinical development, lower manufacturing costs, superior safety and efficacy, lower pricing, stronger patent protection, and better marketing, sales, and distribution capabilities.
Their products may outcompete ours due to one or more factors, including faster progress through preclinical and clinical development, lower manufacturing costs, superior safety and efficacy, lower pricing, stronger patent protection, and better marketing, sales, and distribution capabilities.
If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations. • Phase 3 - undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites.
If a compound demonstrates evidence of efficacy and an acceptable safety profile in Phase 2 evaluations. • Phase 3 - undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites.
The CTD indeed introduced the first set of harmonized rules on clinical trials in the EU but resulted in a patchwork of different national regimes. The CTR was adopted with a view to introducing a more uniform set of the rules across the EU for the authorization of clinical trials.
The CTD indeed introduced the first set of harmonized rules on clinical trials in the EU but resulted in a patchwork of different national regimes. The CTR was adopted with a view to introducing a more uniform set of the rules across the EU for the authorization of 14 clinical trials.
However, generic versions of KUVAN are available in several countries around the world, including multiple generic versions in the U.S. and the EU. Several generic versions of KUVAN have also been approved either centrally by the EC or on a country-by-country basis throughout the EU.
Generic versions of KUVAN are available in several countries around the world, including multiple generic versions in the U.S. and the EU. Several generic versions of KUVAN have also been approved either centrally by the EC or on a country-by-country basis throughout the EU.
Typically, we undertake a three-phase human clinical testing program as follows: • Phase 1 - the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses and, if possible, early evidence on effectiveness. • Phase 2 - usually involves trials in a limited patient population, to determine the effectiveness of the drug for a particular indication or indications, dosage tolerance and optimum dosage, and to identify common adverse effects and safety risks.
Typically, we undertake a three-phase human clinical testing program as follows: • Phase 1 - the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses and, if possible, early evidence on efficacy. • Phase 2 - usually involves trials in a limited patient population, to determine the efficacy of the drug for a particular indication or indications, dosage tolerance and optimum dosage, and to identify common adverse effects and safety risks.
The MAA for the product must include the results of pediatric clinical trials conducted in accordance with the PIP, unless a waiver applies, or a deferral has been granted, in which case the pediatric clinical trials must be completed at a later date.
The 24 MAA for the product must include the results of pediatric clinical trials conducted in accordance with the PIP, unless a waiver applies, or a deferral has been granted, in which case the pediatric clinical trials must be completed at a later date.
In addition to retroactive rebates, if a manufacturer were found to have knowingly submitted false information to the government, federal law provides for civil monetary penalties for failing to provide required information, late submission of required information, and false information.
In addition to retroactive rebates, if a manufacturer were found to have knowingly submitted false information to the government, federal law provides for civil monetary penalties for failing to provide required information, late 22 submission of required information, and false information.
In addition, BMN 351 could have potential competition from clinical product candidates for exon 51 skipping amenable DMD by Dyne Therapeutics, Inc. and PepGen, Inc., and gene therapy product candidates from Regenxbio, Inc. and Solid Biosciences, Inc.
In addition, BMN 351 could have potential competition from clinical product candidates for exon 51 skipping amenable DMD by Dyne Therapeutics, Inc. and gene therapy product candidates from Regenxbio, Inc. and Solid Biosciences, Inc.
Measures required to ensure that include: a unique identifier and an anti-tampering device on the outer packaging of drugs, stringent rules on import of active pharmaceutical ingredients and record-keeping requirements for wholesale distributors. 17 Approval Regulation Outside of the U.S. and the EU For marketing outside the U.S. and the EU, we are subject to non-U.S. regulatory requirements governing human clinical testing and marketing approval for our products.
Measures required to ensure that include: a unique identifier and an anti-tampering device on the outer packaging of drugs, stringent rules on import of active pharmaceutical ingredients and record-keeping requirements for wholesale distributors. 18 Approval Regulation Outside of the U.S. and the EU For marketing outside the U.S. and the EU, we are subject to non-U.S. regulatory requirements governing human clinical testing and marketing approval for our products.
VOXZOGO VOXZOGO, for the treatment of achondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S, QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), Ribomic Inc., Tyra Biosciences Inc., and preclinical product candidates from other companies, including Abbisko Therapeutics Co Ltd, C-Biomex Co., Ltd, Changchun GeneScience Pharmaceuticals Co., Ltd., Immunoforge, Co.
VOXZOGO VOXZOGO, for the treatment of achondroplasia, could have competition from clinical stage products under development by Abbisko Therapeutics Co Ltd., Ascendis Pharma A/S, QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), Ribomic Inc., Tyra Biosciences Inc., and preclinical product candidates from other companies, including Black Diamond Therapeutics, Inc., C-Biomex Co., Ltd., Changchun GeneScience Pharmaceuticals Co., Ltd., Immunoforge, Co.
The FDA and other regulatory agencies around the world conduct regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an initial approval. 16 Combination Products and Companion Diagnostics Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a device).
The FDA and other regulatory agencies around the world conduct regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an initial approval. 17 Combination Products and Companion Diagnostics Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a device).
The CTR established a centralized application procedure where one of the National Competent Authorities (NCA) of the Member States where the trial will take place takes the lead in reviewing certain aspects of the application, while the other NCAs have a lesser involvement than they had under the previous regime established by Directive 2001/20/EC (CTD).
The CTR established a centralized application procedure where one of the National Competent Authorities (NCA) of the Member States where the trial takes place takes the lead in reviewing certain aspects of the application, while the other NCAs have a lesser involvement than they had under the previous regime established by Directive 2001/20/EC (CTD).
This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and 19 prescribers, purchasers and formulary managers on the other.
This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other.
We continue to pursue additional patents and patent term extensions in the U.S. and other 11 territories covering various aspects of our products that may, if issued, extend patent exclusivity beyond the expiration dates listed in the table below. Product Territory Patent No(s).
We continue to pursue additional patents and patent term extensions in the U.S. and other territories covering various aspects of our products that may, if issued, extend patent exclusivity beyond the expiration dates listed in the table below. 12 Product Territory Patent No(s).
U.S. Federal Contracting and Pricing Requirements Manufacturers are also required to make their covered drugs, which are generally drugs approved under NDAs or BLAs, available to authorized users of the Federal Supply Schedule (FSS), which is administered by the Department of Veterans Affairs.
Federal Contracting and Pricing Requirements Manufacturers are also required to make their covered drugs, which are generally drugs approved under NDAs or BLAs, available to authorized users of the Federal Supply Schedule (FSS), which is administered by the Department of Veterans Affairs.
Such reports and other information may be accessed through the SEC’s website at www.sec.gov. Information contained in our website is not part of this or any other report that we file with or furnish to the SEC. 25
Such reports and other information may be accessed through the SEC’s website at www.sec.gov. Information contained in our website is not part of this or any other report that we file with or furnish to the SEC. 26
Other than ROCTAVIAN and KUVAN, as described below, our products have no direct approved competition currently on the market in the U.S. or the EU; however, other companies are in the development phase with new and generic products.
Other than PALYNZIQ and KUVAN, as described below, our products have no direct approved competition currently on the market in the U.S. or the EU; however, other companies are in the development phase with new and generic products.
Clinical trials must be conducted in compliance with applicable regulations, good clinical practices (GCP), as well as under protocols detailing the objectives of the trial and the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.
Clinical trials must be conducted in compliance with applicable regulations, good clinical practices (GCP), as well as under protocols detailing the objectives of the trial and the parameters to be used in monitoring safety and the efficacy criteria to be evaluated.
This is confirmed in the CTR, the new EU legislation on clinical trials, according to which clinical trial applications and all the related documentation are uploaded and stored in the Clinical Trials Information System (CTIS) which is managed by the EMA.
This is confirmed in the CTR, the current EU legislation on clinical trials, according to which clinical trial applications and all the related documentation are uploaded and stored in the Clinical Trials Information System (CTIS) which is managed by the EMA.
The review of these in vitro companion diagnostics in conjunction with the review of a drug or biologic involves coordination of review by the FDA’s Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research and by the FDA’s Center for Devices and Radiological Health.
The review of these in vitro companion diagnostics in conjunction with the review of a drug or biologic involves coordination of review by the FDA’s Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research, as applicable, and by the FDA’s Center for Devices and Radiological Health.
The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it can be demonstrated on the basis of available evidence that the criteria for its designation as an orphan medicine are no longer satisfied, for example if the original orphan medicinal product has become sufficiently profitable not to justify maintenance of market exclusivity.
The period of market exclusivity may, in addition, be reduced to six years if, at the end of the fifth year, it is established on the basis of available evidence that the criteria for its designation as an orphan medicine are no longer satisfied, for example if the original orphan medicinal product has become sufficiently profitable not to justify maintenance of market exclusivity.
Orphan drug exclusive marketing rights obtained upon approval of an orphan-designated drug may be lost under certain conditions, such as if the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug.
In the U.S., orphan drug exclusive marketing rights obtained upon approval of an orphan-designated drug may be lost under certain conditions, such as if the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug.
Governments may regulate access to, prices of or reimbursement levels for our products to control costs or to affect levels of use of our products, and private insurers may be influenced by government reimbursement methodologies. 20 Third-party payers carefully review and increasingly challenge the prices charged for drugs, examine their medical necessity, and review their cost effectiveness.
Governments may regulate access to, prices of or reimbursement levels for our products to control costs or to affect levels of use of our products, and private insurers may be influenced by government reimbursement methodologies. In the U.S., third-party payers carefully review and increasingly challenge the prices charged for drugs, examine their medical necessity, and review their cost effectiveness.
The CTR also established an EU Portal which will act as a single-entry point for submission of data and information relating to clinical trials. Until January 30, 2025, the CTD will continue to apply in parallel to the CTR for a transitional period. From January 31, 2025 all trials will have to comply with the CTR.
The CTR also established an EU Portal which will act as a single-entry point for submission of data and information relating to clinical trials. Until January 30, 2025, the CTD continued to apply in parallel to the CTR for a transitional period. From January 31, 2025 all trials must comply with the CTR.
VOXZOGO, for the treatment of Noonan syndrome, Turner syndrome, and SHOX deficiency could have competition from marketed branded and generic human growth hormones, clinical stage products (marketed for other indications) under development by Ascendis Pharma A/S and Novo Nordisk A/S, an additional clinical stage product from Changchun GeneScience Pharmaceuticals Co., Ltd., and a preclinical product candidate from Cavalry Biosciences.
VOXZOGO, for the treatment of Noonan syndrome, Turner syndrome, and SHOX deficiency could have competition from marketed branded and generic human growth hormones, marketed small molecule tyrosine kinase inhibitors, clinical stage products (marketed for other indications) under development by Ascendis Pharma A/S and Novo Nordisk A/S, an additional clinical stage product from Changchun GeneScience Pharmaceuticals Co., Ltd., and a preclinical product candidate from Cavalry Biosciences.
In the U.S., PALYNZIQ is only available through the PALYNZIQ Risk Evaluation and Mitigation Strategy (REMS) program, which is required by the U.S. Food and Drug Administration (FDA) to mitigate the risk of anaphylaxis while using the product.
In the U.S., PALYNZIQ is only available through the PALYNZIQ Risk Evaluation and Mitigation Strategy (REMS) program, which is required by the FDA to mitigate the risk of anaphylaxis while using the product.
Similar laws exist in other countries, such as the U.K., that restrict improper payments to public and private parties. Many countries have laws prohibiting these types of payments within the respective country.
Similar laws exist in other countries, such as the U.K., that restrict improper payments in the public and private sectors. Many countries have laws prohibiting these types of payments within the respective country.
ALDURAZYME is approved for marketing in the U.S., the EU and other international markets. KUVAN KUVAN is a proprietary synthetic oral form of 6R-BH4, a naturally occurring enzyme co-factor for PAH, indicated for patients with PKU. KUVAN is the first drug for the treatment of PKU, which is an inherited metabolic disease.
BRINEURA is approved for marketing in the U.S. and in the EU for children of all ages and in other international markets. KUVAN KUVAN is a proprietary synthetic oral form of 6R-BH4, a naturally occurring enzyme co-factor for PAH, indicated for patients with PKU. KUVAN is the first drug for the treatment of PKU, which is an inherited metabolic disease.
(5) We applied for SPCs for this patent, and we have to date received SPC to extend the patent expiration to April 30, 2029 in certain European countries, including Austria, Belgium, Bulgaria, Cypress, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain, Sweden, Switzerland and the United Kingdom.
(3) For VIMIZIM, we applied for SPCs for this patent, and to date have been granted SPCs to extend the patent expiration to April 30, 2029 in certain European countries, including Austria, Belgium, Bulgaria, Cypress, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain, Sweden, Switzerland and the United Kingdom.
(2) We applied for SPCs for this patent, and we have to date received SPC to extend the patent expiration to May 23, 2033 in certain European countries, including Austria, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland France, Germany, Greece, Hungary, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Spain, Slovakia, Slovenia, Sweden, and United Kingdom.
(2) For PALYNZIQ, we applied for SPCs for EP 2152868, and to date have been granted SPC to extend the patent expiration to May 23, 2033 in certain European countries, including Austria, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland France, Germany, Greece, Hungary, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Spain, Slovakia, Slovenia, Sweden, and United Kingdom.
The timing of these orders can be inconsistent and can create significant quarter to quarter variation in our revenue. PALYNZIQ is currently distributed in the U.S. pursuant to the REMS program through a limited number of certified specialty pharmacies. During 2024, 25% of our net product revenue was generated by two customers.
The timing of these orders can be inconsistent and can create significant quarter to quarter variation in our revenue. PALYNZIQ is currently distributed in the U.S. pursuant to the REMS program through a limited number of certified specialty pharmacies. During 2025, 37% of our net product revenue was generated by three customers.
For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced. CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027.
For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced.
Ltd., Novo Nordisk A/S, Peptron Inc., Prolynx Inc., and SiSaf Ltd. ALDURAZYME, NAGLAZYME, and VIMIZIM In the mucopolysaccharidosis field, several companies are researching treatments using small molecules, gene therapy, and other novel technologies.
Ltd., Peptron Inc., Prolynx Inc., and SiSaf Ltd. ALDURAZYME, NAGLAZYME, and VIMIZIM In the mucopolysaccharidosis field, several companies are researching treatments using small molecules, gene therapy, and other novel technologies.
Ltd., Novo Nordisk A/S, Peptron Inc., Prolynx Inc., and SiSaf Ltd. BMN 333, for the treatment of hypochondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S and QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), and a preclinical product candidate from Tyra Biosciences Inc.
BMN 333, for the treatment of hypochondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S and QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), and a preclinical product candidate from Tyra Biosciences Inc.
In addition to patent protection, certain of our products are entitled to regulatory exclusivity in the U.S. and the EU through the dates set forth below: Commercial Products United States Orphan Drug Exclusivity Expiration (1) United States Biologic Exclusivity Expiration (2) European Union Orphan Drug Exclusivity Expiration (1) BRINEURA 2031 (3) 2029 2029 PALYNZIQ 2025 2030 2029 ROCTAVIAN 2030 2035 2032 VIMIZIM Expired 2026 2026 VOXZOGO 2030 (4) Not Applicable 2031 (1) See “Government Regulation—Other Regulation—Orphan Drug Designation” in this Annual Report on Form 10-K for further discussion.
PTE has been granted in Australia and Japan to May 20, 2035. 13 In addition to patent protection, certain of our products are entitled to regulatory exclusivity in the U.S. and the EU through the dates set forth below: Commercial Products United States Orphan Drug Exclusivity Expiration (1) United States Biologic Exclusivity Expiration (2) European Union Orphan Drug Exclusivity Expiration (1) BRINEURA 2031 (3) 2029 2029 PALYNZIQ Expired 2030 2029 VIMIZIM Expired 2026 Expired VOXZOGO 2030 (4) Not Applicable 2031 (1) See “Government Regulation—Other Regulation—Orphan Drug Designation” in this Annual Report on Form 10-K for further discussion.
Additionally, we are, or may become, subject to various U.S. federal and state consumer protection laws which require us to publish statements that accurately and fairly describe how we handle personal data and choices individuals may have about the way we handle their personal data.
Additionally, various U.S. federal and state consumer protection laws which require us to publish statements that accurately and fairly describe how we handle personal data and choices individuals may have about their personal data.
There must be no differences in route of administration, dosage form, and strength to rely on a given reference product, and there can be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency.
There must be no differences in route of administration, dosage form, and strength to rely on a given reference product, and there can be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency. Biosimilarity must be shown through analytical studies and animal studies.
In certain circumstances, disclosure of the results of these trials can be delayed for up to two years after the date of completion of the trial. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.
Sponsors are also obligated to discuss the results of their clinical trials after completion. In certain circumstances, disclosure of the results of these trials can be delayed for up to two years after the date of completion of the trial. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.
On January 31, 2022, Regulation EU No 536/2014 (CTR) became fully 13 applicable in the EU.
On January 31, 2022, Regulation EU No 536/2014 (CTR) became fully effective in the EU.
Sales and Marketing We have established a commercial organization, which starting in 2025, is primarily structured around three business units: Skeletal Conditions, Enzyme Therapies and ROCTAVIAN. This organization, which includes a sales force, supports our product lines directly in the U.S., Europe, South America and certain other significant markets.
Sales and Marketing Our commercial organization is primarily structured around two business units: Skeletal Conditions (VOXZOGO) and Enzyme Therapies. This organization, which includes a sales force, supports our product lines directly in the U.S., Europe, South America and certain other significant markets.
It is illegal to pay, offer to pay or authorize the payment of anything of value to any non-U.S. government official, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.
It is illegal to pay, provide offer to pay or authorize the provision of anything of value to any non-U.S. government official, government staff member, employee or officer of a state-owned or controlled entity, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity.
(a subsidiary of BridgeBio Pharma, Inc.), and a preclinical product candidate from Tyra Biosciences Inc. 10 VOXZOGO, for the treatment of idiopathic short stature could have competition from marketed branded and generic human growth hormones, clinical stage products (marketed for other indications) under development by Ascendis Pharma A/S, and Novo Nordisk A/S, and additional clinical stage products by Anhui Anke Biotechnology (Group) Co., Ltd. and Changchun GeneScience Pharmaceuticals Co., Ltd.
VOXZOGO, for the treatment of idiopathic short stature could have competition from marketed branded and generic human growth hormones, clinical stage products (marketed for other indications) under development by Ascendis Pharma A/S, and Novo Nordisk A/S, and additional clinical stage products by Anhui Anke Biotechnology (Group) Co., Ltd., Xiamen Amoytop Biotech Co., Ltd. and Changchun GeneScience Pharmaceuticals Co., Ltd. as well as a preclinical stage product from Bolder BioTechnology, Inc.
The out-of-pocket limit is $2,000 in 2025 and is to be adjusted for inflation thereafter.
The out-of-pocket limit is $2,100 in 2026 and is to be adjusted for inflation thereafter.
Research and Development Programs VOXZOGO VOXZOGO, for the treatment of hypochondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S and QED Therapeutics, Inc.
Research and Development Programs VOXZOGO VOXZOGO, for the treatment of hypochondroplasia, could have competition from clinical stage products under development by Ascendis Pharma A/S and QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), and a preclinical product candidate from Tyra Biosciences Inc.
The launch of any future products, if approved, will likely require expansion of our commercial organization, including our sales force, in the U.S. and international markets. We utilize third-party logistics companies to store and distribute our products.
The launch of any future products, if approved, or for the 9 sales and marketing of products that we acquire through strategic transactions, will likely require expansion of our commercial organization, including our sales force, in the U.S. and international markets. We utilize third-party logistics companies to store and distribute our products.
We completed the single-ascending dose phase of the first-in-human study and dosing in the multiple-ascending dose phase of the study began in December 2024. BMN 351 BMN 351 is our next-generation oligonucleotide in development for the treatment of Duchenne Muscular Dystrophy (DMD). We completed enrollment into the first and second dose cohorts in late 2024.
BMN 351 BMN 351 is our next-generation oligonucleotide in development for the treatment of Duchenne Muscular Dystrophy (DMD). We completed enrollment into the first and second dose cohorts in late 2024.
In patients with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 gene (FGFR3).
In patients with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 gene (FGFR3). VOXZOGO acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.
We believe that with moderate changes in 2025, including changes in connection with the reorganization of the commercial organization described above, the size of our sales force will be appropriate to effectively reach our target customers in markets where our products are directly marketed.
We believe that with moderate changes in 2026, the size of our sales force will be appropriate to effectively reach our target customers in markets where our products are directly marketed.
However, if an orphan drug later receives approval for the indication for which it has designation, the relevant regulatory authority may not approve any other applications to market the same drug for the same condition, except in limited circumstances, for seven years in the U.S. and ten years in the EU (extendable to twelve years for medicines that have complied with an agreed Pediatric Investigation Plan (PIP) pursuant to Regulation 1901/2006) and, in addition, a range of other benefits during the development and regulatory review process are available in the EU, including scientific assistance for study protocols, authorization through the centralized marketing authorization procedure covering all member countries and a reduction or elimination of registration and marketing authorization fees.
However, if an orphan drug later receives approval for the indication for which it has designation, under the current rules, the relevant regulatory authority may not accept or approve any other applications to market a similar medicinal product/drug for the same therapeutic indication, except in limited circumstances, for seven years in the U.S. and ten years in the EU (extendable to twelve years under certain circumstances) and, in addition, a range of other benefits during the development and regulatory review process are available in the EU, including scientific assistance for study protocols, authorization through the centralized marketing authorization procedure covering all member countries and a reduction or elimination of registration and marketing authorization fees.
U.S. patents that were issued on applications filed before June 8, 1995, may be effective until 17 years from the issue date, if that is later than the 20-year date.
U.S. patents, as well as most foreign patents, are generally effective for 20 years from the date the earliest application was filed. U.S. patents that were issued on applications filed before June 8, 1995, may be effective until 17 years from the issue date, if that is later than the 20-year date.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks related to the commercialization of ROCTAVIAN.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks posed by the REMS program.
Of the 3,040 employees as of December 31, 2024, 1,917 employees were in the U.S. and Canada, and 1,123 employees were outside of North America, including 920 in Europe and the Middle East, 131 in Latin America and 72 in Asia Pacific. We also leverage temporary workers to fill short-term positions for our business and manufacturing needs.
Of the 3,221 employees as of December 31, 2025, 2,026 employees were in the U.S. and Canada, and 1,195 employees were outside of North America, including 967 in Europe and the Middle East, 151 in Latin America and 77 in Asia Pacific. We also leverage temporary workers to fill short-term positions for our business and manufacturing needs.
Among the remedies available to the government for any failure to properly disclose commercial pricing and/or to extend FSS contract price reductions is recoupment of any FSS overcharges that may result from such omissions, and civil penalties under the Federal False Claims Act if such failures are knowing. 22 Disclosure of Clinical Trial Information Sponsors of clinical trials of FDA-regulated products, including drugs and biologics, are required to register and disclose certain clinical trial information.
Among the remedies available to the government for any failure to properly disclose commercial pricing and/or to extend FSS contract price reductions is recoupment of any FSS overcharges that may result from such omissions, and civil penalties under the Federal False Claims Act if such failures are knowing.
We believe that approximately 30% to 50% of those with PKU could benefit from treatment with KUVAN. KUVAN is approved for marketing in the U.S., the EU and other international markets (excluding Japan). In certain international markets, KUVAN is also approved for, or is only approved for, the treatment of primary BH4 deficiency, a different disorder than PKU.
KUVAN is approved for marketing in the U.S., the EU and other international markets (excluding Japan). In certain international markets, KUVAN is also approved for, or is only approved for, the treatment of primary BH4 deficiency, a different disorder than PKU.
Breakthrough Therapy Designation The FDA is also required to expedite the development and review of the application for approval of drugs that are intended to treat a serious or life-threatening disease or condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
The FDA may initiate enforcement action for the failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports. 16 Breakthrough Therapy Designation The FDA is also required to expedite the development and review of the application for approval of drugs that are intended to treat a serious or life-threatening disease or condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
BRINEURA is the first treatment approved to slow the progression of loss of ambulation in children with CLN2 disease and was one of the first therapies to go through an accelerated review procedure in the EU.
Patients are initially healthy but begin to decline at approximately the age of three. BRINEURA is the first treatment approved to 7 slow the progression of loss of ambulation in children with CLN2 disease and was one of the first therapies to go through an accelerated review procedure in the EU.
FDORA also requires the FDA to specify conditions of any required post-approval study, which may include milestones such as a target date of study completion and requires sponsors to submit progress reports for required post-approval studies and any conditions required by the FDA not later than 180 days following approval and not less frequently than every 180 days thereafter until completion or termination of the study.
Sponsors are required to submit progress reports for required post-approval studies and any conditions required by the FDA not later than 180 days following approval and not less frequently than every 180 days thereafter until completion or termination of the study.
HRSA has also issued regulations relating to the calculation of the ceiling price as well as imposition of civil monetary penalties for each instance of knowingly and intentionally overcharging a 340B covered entity.
Manufacturers are required to report pricing information to the Health Resources and Services Administration (HRSA) on a quarterly basis. HRSA has also issued regulations relating to the calculation of the ceiling price as well as imposition of civil monetary penalties for each instance of knowingly and intentionally overcharging a 340B covered entity.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks posed by generic versions of KUVAN in the U.S. and international markets. PALYNZIQ and KUVAN also have potential competition from clinical stage product candidates from Agios Pharmaceuticals Inc., Jnana Therapeutics Inc.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks posed by generic versions of KUVAN in the U.S. and international markets.
VOXZOGO acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. 5 VOXZOGO is approved for marketing in the U.S. and Japan for the treatment of achondroplasia in children with open growth plates of all ages, in the EU for the treatment of children with open growth plates aged four months and older, and in other markets, including Australia and Brazil, for patients in various age ranges.
VOXZOGO is approved for marketing in the U.S. and Japan for the treatment of achondroplasia in children with open growth plates of all ages, in the European Union (EU) for the treatment of children with open growth plates aged four months and older, and in other markets, including Australia and Brazil, for patients in various age ranges.
Foreign Corrupt Practices Act (FCPA), to which we are subject, prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity.
Foreign Corrupt Practices Act (FCPA), to which we are subject, prohibits U.S. persons, including U.S. entities and their employees, officers, and intermediaries from engaging in certain activities, directly or indirectly, to obtain or retain business or to influence a person working in an official capacity.
We are also subject to the EU’s General Data Protection Regulation GDPR, which requires that personal data is only collected for specified, explicit and legal purposes as set out in the GDPR or local laws, and the data may then only be processed in a manner consistent with those purposes.
Outside of the United States, the EU’s General Data Protection Regulation (EU GDPR) and UK's General Data Protection Regulation (UK GDPR and collectively, GDPR), which require, among other things, that personal data is only collected for specified, explicit and legal purposes as set out in the GDPR or local laws, and the data may then only be processed in a manner consistent with those purposes.
MPS I is a progressive and debilitating life-threatening genetic disease that is caused by the deficiency of alpha-L-iduronidase. Patients with MPS I typically become progressively worse and experience multiple severe and debilitating symptoms resulting from the build-up of carbohydrate residues in all tissues in the body.
Patients with MPS I typically become progressively worse and experience multiple severe and debilitating symptoms resulting from the build-up of carbohydrate residues in all tissues in the body.
Human Capital As of December 31, 2024, we had 3,040 employees worldwide, of whom 1,472 were in operations, 635 were in research and development, 458 were in sales and marketing and 475 were in administration.
Human Capital As of December 31, 2025, we had 3,221 employees worldwide, of whom 1,518 were in operations, 692 were in research and development, 495 were in sales and marketing and 516 were in administration.
Recent Developments In 2024, we achieved $2.9 billion in total revenues, including a significant contribution from our ongoing expansion of VOXZOGO, and we continued making important advancements in our product development pipeline.
Recent Developments In 2025, we achieved $3.2 billion in total revenues, including a significant contribution from our ongoing expansion of VOXZOGO, and we continued to grow our commercial business and advance our product candidate pipeline.
BMN 333 BMN 333 is a longer-acting CNP in development for the treatment of multiple growth disorders, including achondroplasia and hypochondroplasia. We initiated the first-in-human study of BMN 333 in January 2025. BMN 349 BMN 349 is an oral therapeutic in development for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency.
BMN 333 BMN 333 is a longer-acting CNP in development for the treatment of multiple growth disorders, including achondroplasia and hypochondroplasia. We initiated the first-in-human study of BMN 333 in January 2025. In 2025, we accelerated development of BMN 333 with Phase 1 pharmacokinetic data exceeding targeted free CNP exposure levels.
All of our facilities and those of any third-party manufacturers will be subject to periodic inspections confirming compliance with applicable law and must pass inspection before we can manufacture our drugs for commercial sale. Third-party manufacturers’ facilities are subject to periodic inspections to confirm compliance with applicable law and must be cGMP certified.
We expect to continue to contract with outside service providers for certain manufacturing services, including drug substance, drug product, and packaging operations for our products. All of our facilities and those of any third-party manufacturers will be subject to periodic inspections confirming compliance with applicable law and must pass inspection before we can manufacture our drugs for commercial sale.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks related to VOXZOGO in the U.S. and international markets. NAGLAZYME NAGLAZYME is a recombinant form of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) indicated for patients with MPS VI.
Please see “Risk Factors” included in Part I, Item 1A of this Annual Report on Form 10-K for a discussion of the risks related to VOXZOGO in the U.S. and international markets. VIMIZIM VIMIZIM is an enzyme replacement therapy for the treatment of MPS IVA, a lysosomal storage disorder.
BMN 333 BMN 333, for the treatment of achondroplasia could have competition from clinical stage products under development by Ascendis Pharma A/S, QED Therapeutics, Inc. (a subsidiary of BridgeBio Pharma, Inc.), Ribomic Inc., Tyra Biosciences Inc., and preclinical product candidates from other companies, including Abbisko Therapeutics Co Ltd, C-Biomex Co., Ltd, Changchun GeneScience Pharmaceuticals Co., Ltd., Immunoforge, Co.
BMN 333 BMN 333, for the treatment of achondroplasia could have competition from clinical stage products under development by Abbisko Therapeutics Co Ltd., Ascendis Pharma A/S, QED Therapeutics, Inc.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThese proposals are based on two “pillars”, Pillar One focuses on the allocation of taxing rights in respect of certain profits of multinational enterprises with annual global revenue above 20 billion euros and profitability above 10% to the jurisdictions within which they carry on business (based on the thresholds, we currently expect to be outside the scope of the Pillar One proposals, but could fall within their scope in the future) and Pillar Two imposes a minimum effective tax rate of 15% on certain multinational enterprises that have consolidated revenues of at least 750 million euros in at least two out of the last four years (based on the thresholds, we currently expect that we are likely to fall within the scope of the Pillar Two proposals).
Biggest changeThese proposals include, among other measures, the imposition of a minimum effective tax rate of 15% on certain multinational enterprises that have consolidated revenues of at least 750 million euros in at least two out of the last four years.
Government price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our current and future products, which would adversely affect our revenues and results of operations. We expect that coverage and reimbursement may be increasingly restricted in all the markets in which we sell our products.
Government price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our current and future products, which would adversely affect our revenues and results of operations. We expect that pricing, coverage and reimbursement may be increasingly restricted in all the markets in which we sell our products.
If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including by limiting our ability to conduct clinical trial activities in Europe and elsewhere, the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of 50 personal data necessary to operate our business.
If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including by limiting our ability to conduct clinical trial activities in Europe and elsewhere, the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.
In the EU, pursuant to the Regulation (EC) No. 141/2000 (the Orphan Regulation), as implemented by Regulation (EC) No. 847/2000, orphan drug designation is available if a sponsor can establish that: (1) the medicine is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 people in the EU at the time the application is made, or, (2) that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives derived from the orphan status, it is unlikely that the marketing of the medicine in the EU would generate sufficient return to justify the necessary investment.
In the EU, pursuant to the Regulation (EC) No. 141/2000 (the Orphan Regulation), as implemented by Regulation (EC) No. 847/2000, orphan drug designation is available if a sponsor can establish that: (1) the medicine is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 people in the EU at the time the application is made, or, (2) that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives derived from the orphan status, it is unlikely that the marketing of the medicine in the EU would generate 38 sufficient return to justify the necessary investment.
Cybersecurity incidents resulting in the failure of our ERP system, production management or other systems to operate effectively or to integrate with other systems, or a breach in security or other unauthorized access or unavailability of these systems or those of any third parties in our supply chain or on whom we otherwise depend, have occurred in the past and may affect our ability in the future to manage and maintain our operations, inventory and internal reports, and result in delays in product fulfillment and reduced efficiency of our operations.
Cybersecurity incidents resulting in the failure of our ERP system, production management or other systems to operate effectively or to integrate with other systems, or a breach in security or other unauthorized access or unavailability of these 56 systems or those of any third parties in our supply chain or on whom we otherwise depend, have occurred in the past and may affect our ability in the future to manage and maintain our operations, inventory and internal reports, and result in delays in product fulfillment and reduced efficiency of our operations.
Trade restrictions and export regulations, or increases in tariffs and additional taxes, including any retaliatory measures, can negatively impact demand, increase our supply chain complexity and our manufacturing costs, decrease margins, reduce the competitiveness of our products, or restrict our ability to sell products, provide services or purchase necessary equipment and supplies, any or all of which could have a material and adverse effect on our business, results of operations, or financial condition.
Trade restrictions and export regulations, or increases in tariffs and additional taxes, including any retaliatory measures, could negatively impact demand, increase our supply chain complexity and our manufacturing costs, decrease margins, reduce the competitiveness of our products, or restrict our ability to sell products, provide services or purchase necessary equipment and supplies, any or all of which could have a material and adverse effect on our business, results of operations, or financial condition.
In the U.S., the federal Anti-Kickback Statute makes it illegal for any person or entity, including a pharmaceutical company, to knowingly and willfully offer, solicit, pay or receive any remuneration, directly or indirectly, in exchange for or to induce the referral of business, including the purchase, order or prescription of a particular drug, for which payment may be made under federal healthcare programs, such as Medicare and 48 Medicaid.
In the U.S., the federal Anti-Kickback Statute makes it illegal for any person or entity, including a pharmaceutical company, to knowingly and willfully offer, solicit, pay or receive any remuneration, directly or indirectly, in exchange for or to induce the referral of business, including the purchase, order or prescription of a particular drug, for which payment may be made under federal healthcare programs, such as Medicare and Medicaid.
For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information. Additionally, numerous U.S. states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information. Additionally, numerous 54 U.S. states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
Although the FDA and other comparable international and national regulatory 31 authorities do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
Although the FDA and other comparable international and national regulatory authorities do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
Investigations of any actual or alleged violations of such laws or policies related to us could harm our business, financial condition, results of operations, cash flows and prospects. Moreover, there has been enhanced scrutiny of company-sponsored patient assistance programs, including insurance premium and co-pay assistance programs and donations to third-party independent charities that provide such assistance.
Investigations of any actual or alleged violations of such laws or policies related to us could harm our business, financial condition, results of operations, cash flows and prospects. 46 Moreover, there has been enhanced scrutiny of company-sponsored patient assistance programs, including insurance premium and co-pay assistance programs and donations to third-party independent charities that provide such assistance.
Moreover, follow-on manufacturers, including generic and biosimilar manufacturers, may use litigation and regulatory means to obtain approval for generic, biosimilar, or other follow-on versions of our products notwithstanding our filed patents or patent applications. 44 If we are unable to protect our intellectual property, third parties could develop competing products, which could adversely affect our revenues and financial results generally.
Moreover, follow-on manufacturers, including generic and biosimilar manufacturers, may use litigation and regulatory means to obtain approval for generic, biosimilar, or other follow-on versions of our products notwithstanding our filed patents or patent applications. If we are unable to protect our intellectual property, third parties could develop competing products, which could adversely affect our revenues and financial results generally.
If we do not obtain orphan drug designation and related regulatory exclusivity for our products that do not have broad patent protection or if a competing product is determined to be, for example, "clinically superior" to any of our 35 products that has secured orphan drug exclusivity, our competitors may then sell the same drug to treat the same condition and our revenues will be reduced.
If we do not obtain orphan drug designation and related regulatory exclusivity for our products that do not have broad patent protection or if a competing product is determined to be, for example, "clinically superior" to any of our products that has secured orphan drug exclusivity, our competitors may then sell the same drug to treat the same condition and our revenues will be reduced.
In the EU, a medicinal product containing a new active substance benefits from eight years of data exclusivity, during which biosimilar applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which biosimilar applications may be submitted and the reference product's data may be referenced but biosimilar products may not be placed on the market.
In the EU, a medicinal product containing a new active substance currently benefits from eight years of data exclusivity, during which biosimilar applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which biosimilar applications may be submitted and the reference product's data may be referenced but biosimilar products may not be placed on the market.
If we are unable to successfully develop and maintain manufacturing processes for our product candidates to produce sufficient quantities at acceptable costs, we may be unable to support a clinical trial or be forced to terminate a 38 program, or if we are unable to produce sufficient quantities of our products at acceptable costs, we may be unable to meet commercial demand, lose potential revenue, have reduced margins or be forced to terminate a program.
If we are unable to successfully develop and maintain manufacturing processes for our product candidates to produce sufficient quantities at acceptable costs, we may be unable to support a clinical trial or be forced to terminate a program, or if we are unable to produce sufficient quantities of our products at acceptable costs, we may be unable to meet commercial demand, lose potential revenue, have reduced margins or be forced to terminate a program.
In addition, because the number of potential patients in each disease population is small, it is not only important to find patients who begin therapy to achieve significant market penetration of the product, but we also need to be able to maintain these patients on therapy for an extended period of time.
In 29 addition, because the number of potential patients in each disease population is small, it is not only important to find patients who begin therapy to achieve significant market penetration of the product, but we also need to be able to maintain these patients on therapy for an extended period of time.
If we must spend significant time and money protecting or enforcing our patents, designing around patents held by others or licensing, potentially for large fees, patents or other proprietary rights held by others, our business and financial prospects may be harmed. 43 The patent positions of biopharmaceutical products are complex and uncertain.
If we must spend significant time and money protecting or enforcing our patents, designing around patents held by others or licensing, potentially for large fees, patents or other proprietary rights held by others, our business and financial prospects may be harmed. The patent positions of biopharmaceutical products are complex and uncertain.
Increasingly, third-party payers are requiring that drug companies provide them with predetermined discounts from list prices as a condition of coverage, 27 are using restrictive formularies and preferred drug lists to leverage greater discounts in competitive classes, and are challenging the prices charged for medical products.
Increasingly, third-party payers are requiring that drug companies provide them with predetermined discounts from list prices as a condition of coverage, are using restrictive formularies and preferred drug lists to leverage greater discounts in competitive classes, and are challenging the prices charged for medical products.
Our ALDURAZYME, BRINEURA, NAGLAZYME, PALYNZIQ, ROCTAVIAN and VIMIZIM products are regulated by the FDA as biologics under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act (the PHS Act). Biologics require the submission of a Biologics License Application (BLA) and licensure by the FDA prior to being marketed in the U.S.
Our ALDURAZYME, BRINEURA, NAGLAZYME, PALYNZIQ and VIMIZIM products are regulated by the FDA as biologics under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act (the PHS Act). Biologics require the submission of a Biologics License Application (BLA) and licensure by the FDA prior to being marketed in the U.S.
If we do not compete successfully, our revenues would be adversely affected, and we may be unable to generate sufficient sales to recover our expenses related to the development of a product program or to justify continued marketing of a product. We also face competition from generic versions of our products.
If we do not compete successfully, our revenues would be adversely affected, and we may be unable to generate sufficient sales to recover our expenses related to the development of a product program or to justify continued marketing of a product. 28 We also face competition from generic versions of our products.
We have had fewer interactions with regulatory authorities outside the U.S. and the EU as compared to our interactions with the FDA, the EC and the EMA. The approval procedures vary among countries and can involve additional clinical testing, and the time required to obtain approval may differ from that required to obtain FDA or EC approval.
We have had fewer interactions with regulatory authorities outside the U.S. and the EU as compared to our interactions with the FDA, the EC and the EMA. The approval procedures vary among countries and can involve additional clinical testing, and 32 the time required to obtain approval may differ from that required to obtain FDA or EC approval.
However, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in others. The non-U.S. regulatory approval process may include all of the risks associated with obtaining FDA or EC approval. We may not obtain non-U.S. 29 regulatory approvals on a timely basis, if at all.
However, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in others. The non-U.S. regulatory approval process may include all of the risks associated with obtaining FDA or EC approval. We may not obtain non-U.S. regulatory approvals on a timely basis, if at all.
These programs are not well defined in some countries and are subject to changes in requirements, funding levels, unmet medical need and classification of the disease treated by our product. Any change to these programs could adversely affect our 41 ability to sell our products in those countries and delay sales.
These programs are not well defined in some countries and are subject to changes in requirements, funding levels, unmet medical need and classification of the disease treated by our product. Any change to these programs could adversely affect our ability to sell our products in those countries and delay sales.
Delaware law also prohibits corporations from engaging in a 46 business combination with any holders of 15% or more of their capital stock until the holder has held the stock for three years unless, among other possibilities, our Board of Directors approves the transaction.
Delaware law also prohibits corporations from engaging in a business combination with any holders of 15% or more of their capital stock until the holder has held the stock for three years unless, among other possibilities, our Board of Directors approves the transaction.
Due to the breadth of the healthcare laws described above, the narrowness of available statutory and regulatory exceptions and safe harbors and the increased focus by law enforcement authorities in enforcing such laws, our business activities 49 could be subject to challenge under one or more of such laws.
Due to the breadth of the healthcare laws described above, the narrowness of available statutory and regulatory exceptions and safe harbors and the increased focus by law enforcement authorities in enforcing such laws, our business activities could be subject to challenge under one or more of such laws.
Further, Congress and the executive branch have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs. In some international markets, the government controls the pricing, which can affect the profitability of drugs.
Further, Congress and the executive branch have each indicated that they will continue to seek new legislative and/or administrative measures to control 36 drug costs. In some international markets, the government controls the pricing, which can affect the profitability of drugs.
While we could seek to obtain additional third-party financing to pay for any amounts due in cash upon maturity of the 2027 Notes, we cannot be sure that such third-party financing will be available on commercially reasonable terms, if at all.
While we could seek to obtain additional third-party financing to pay for any amounts due in cash upon maturity of the Notes, we cannot be sure that such third-party financing will be available on commercially reasonable terms, if at all.
These exclusive forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage lawsuits against us and our directors, officers, and other employees.
These exclusive forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage lawsuits against us and our directors, 51 officers, and other employees.
Current government regulations and possible future legislation regarding healthcare may affect coverage and reimbursement for medical 33 treatment by third-party payers, which may render our products not commercially viable or may adversely affect our future revenues and gross margins.
Current government regulations and possible future legislation regarding healthcare may affect coverage and reimbursement for medical treatment by third-party payers, which may render our products not commercially viable or may adversely affect our future revenues and gross margins.
We may require additional financing to fund the repayment of the 2027 Notes, future milestone payments and our future operations, including the commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and acquisitions.
We may require additional financing to fund the repayment of the Notes, future milestone payments and our future operations, including the commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and acquisitions.
Due to the complexity of manufacturing our product candidates and products, we may not be able to manufacture sufficient quantities. Our inability to produce enough of our product candidate at acceptable costs may result in the delay or termination of development programs.
Due to the complexity of manufacturing our product candidates and products, we may not be able to manufacture sufficient quantities. Our inability to produce enough of our product candidates at acceptable costs may result in the delay or termination of development programs.
Changes in manufacturing processes (including manufacturing cell lines), equipment or facilities (including moving manufacturing from one of our facilities to another one of our facilities or a third-party facility, or from a third-party facility to one of our facilities) may require us to complete clinical trials to receive regulatory approval of any manufacturing modifications.
Changes in manufacturing processes (including manufacturing cell lines), 42 equipment or facilities (including moving manufacturing from one of our facilities to another one of our facilities or a third-party facility, or from a third-party facility to one of our facilities) may require us to complete clinical trials to receive regulatory approval of any manufacturing modifications.
In addition, because these devices are provided by unaffiliated third-party companies, we are dependent on the sustained cooperation and effort of those third-party companies both to obtain regulatory approval and to maintain their own regulatory compliance.
In addition, because these devices are provided by unaffiliated third-party companies, we are dependent on the sustained 33 cooperation and effort of those third-party companies both to obtain regulatory approval and to maintain their own regulatory compliance.
In addition, the existence of the 2027 Notes may encourage short selling by market participants because the conversion of the 2027 Notes could be used to satisfy short positions, or anticipated conversion of the 2027 Notes into shares of our common stock could depress the price of our common stock.
In addition, the existence of the 2027 Notes may encourage short selling by market participants because the 50 conversion of the 2027 Notes could be used to satisfy short positions, or anticipated conversion of the 2027 Notes into shares of our common stock could depress the price of our common stock.
The insurance that we carry, the inventory that we maintain and our risk mitigation plans may not be adequate to cover our losses resulting from disasters or other business interruptions. 53 Our business is affected by macroeconomic conditions.
The insurance that we carry, the inventory that we maintain and our risk mitigation plans may not be adequate to cover our losses resulting from disasters or other business interruptions. Our business is affected by macroeconomic conditions.
Moreover, promotional communications with respect to prescription drugs, including biologics, are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling and Summary of Product Characteristics.
Moreover, promotional communications with respect to drugs, including biologics, are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling and Summary of Product Characteristics.
To the extent macroeconomic conditions continue to adversely affect our business and financial results, they may also have the effect of heightening many of the other risks described in this Risk Factors section, such as those relating to our conducting a significant amount of our sales and operations outside of the U.S., exposure to changes in foreign exchange rates, our need to generate sufficient cash flows to service our indebtedness and finance our operations and the volatility of our stock price. 54 Item 1B.
To the extent macroeconomic conditions continue to adversely affect our business and financial results, they may also have the effect of heightening many of the other risks described in this Risk Factors section, such as those relating to our conducting a significant amount of our sales and operations outside of the U.S., exposure to changes in foreign exchange rates, our need to generate sufficient cash flows to service our indebtedness and finance our operations and the volatility of our stock price. 59 Item 1B.
The number of preclinical studies and clinical 32 trials that regulatory authorities require varies depending on the product candidate, the disease or condition the drug is being developed to address and regulations applicable to the particular drug.
The number of preclinical studies and clinical trials that regulatory authorities require varies depending on the product candidate, the disease or condition the drug is being developed to address and regulations applicable to the particular drug.
Our manufacturing facilities in the U.S. are licensed for the manufacture of PALYNZIQ, ROCTAVIAN, ALDURAZYME, BRINEURA, NAGLAZYME, VIMIZIM, and VOXZOGO. Our manufacturing facility in Shanbally, Cork, Ireland is licensed for the manufacture of VIMIZIM and BRINEURA and packaging operations for VOXZOGO and PALYNZIQ.
Our manufacturing facilities in the U.S. are licensed for the manufacture of PALYNZIQ, ALDURAZYME, BRINEURA, NAGLAZYME, VIMIZIM, and VOXZOGO. Our manufacturing facility in Shanbally, Cork, Ireland is licensed for the manufacture of VIMIZIM and BRINEURA and packaging operations for VOXZOGO and PALYNZIQ.
In particular, a product may not be promoted for uses that are not approved by the FDA or the EC as reflected in the product’s approved labeling.
In particular, a product may not be promoted for uses that are not approved by the FDA or the EC as reflected in 34 the product’s approved labeling.
We have experienced and may continue to experience security incidents, although to our knowledge we have not experienced any material incident or interruption to date.
We have experienced and may continue to experience security incidents, although 57 to our knowledge we have not experienced any material incident or interruption to date.
In the EU, a ten-year period of market exclusivity for the approved therapeutic indication (extendable to twelve years for orphan drugs that have complied with an agreed Pediatric Investigation Plan (PIP) pursuant to Regulation 1901/2006), during which the EC and EU Member States cannot accept another marketing authorization (MA) application or accept an application to extend existing authorizations for similar medicinal products for the same indication and no MA can be granted.
Under the current rules in the EU, a ten-year period of market exclusivity for the approved therapeutic indication (extendable to twelve years for orphan drugs that have complied with an agreed Pediatric Investigation Plan (PIP) pursuant to Regulation 1901/2006), during which the EC and EU Member States cannot accept another marketing authorization (MA) application or accept an application to extend existing authorizations for similar medicinal products for the same indication and no MA can be granted.
The recent changes in our 47 management team, organizational structure, and corporate strategy could cause retention and morale concerns among current employees, and may create operational risks. The competition for qualified personnel in the pharmaceutical field is intense, and there is a limited pool of qualified potential employees to recruit.
Changes to our management team, organizational structure, and corporate strategy could cause retention and morale concerns among current employees, and may create operational risks. The competition for qualified personnel in the pharmaceutical field is intense, and there is a limited pool of qualified potential employees to recruit.
In order to continue development of such product candidates and marketing of products with larger markets, we will need to continue expanding our operations. To manage expansion effectively, we need to continue to develop and improve our research and development capabilities, manufacturing and quality capacities, sales and marketing capabilities, financial and administrative systems and standard processes for global operations.
In order to continue the development of our product candidates and marketing of products with larger markets, we will need to continue expanding our operations. To manage expansion effectively, we need to continue to develop and improve our research and development capabilities, manufacturing and quality capacities, sales and marketing capabilities, financial and administrative systems and standard processes for global operations.
The amount of capital we will need depends on many factors, including: • our ability to successfully market, protect, and sell our products; • the time and cost necessary to develop commercial manufacturing processes, including quality systems, and to build or acquire manufacturing capabilities the progress and success of our preclinical studies and clinical trials (including studies and the manufacture of materials); • the timing, number, size and scope of our preclinical studies and clinical trials; • the time and cost necessary to obtain regulatory approvals and the costs of post-marketing studies which may be required by regulatory authorities; • the progress of research programs carried out by us; • any changes made to, or new developments in, our existing collaborative, licensing and other commercial relationships or any new collaborative, licensing and other commercial relationships that we may establish; • Sanofi’s ability to continue to successfully commercialize ALDURAZYME; and • whether our convertible debt is converted to common stock in the future.
The amount of capital we will need depends on many factors, including: • our ability to successfully market, protect, and sell our products; • the time and cost necessary to develop commercial manufacturing processes, including quality systems, and to build or acquire manufacturing capabilities the progress and success of our preclinical studies and clinical trials (including studies and the manufacture of materials); • the timing, number, size and scope of our preclinical studies and clinical trials; • our future plans for strategic investments and/or acquisitions; • the time and cost necessary to obtain regulatory approvals and the costs of post-marketing studies which may be required by regulatory authorities; • the progress of research programs carried out by us; • any changes made to, or new developments in, our existing collaborative, licensing and other commercial relationships or any new collaborative, licensing and other commercial relationships that we may establish; • Sanofi’s ability to continue to successfully commercialize ALDURAZYME; and • whether our convertible debt is converted to common stock in the future.
Orphan drug designation neither shortens the development time or regulatory review time of a drug, nor gives the drug any advantage in the regulatory review or approval process. We may face competition from biosimilars approved through an abbreviated regulatory pathway.
Further, orphan drug designation neither shortens the development time or regulatory review time of a drug, nor gives the drug any advantage in the regulatory review or approval process. 39 We may face competition from biosimilars approved through an abbreviated regulatory pathway.
As of December 31, 2024, no amounts were outstanding under the 2024 Credit Facility.
As of December 31, 2025, no amounts were outstanding under the 2024 Credit Facility.
This could result in the delay, reduction or termination of our research, which could harm our business. We have incurred substantial indebtedness that may decrease our business flexibility, access to capital, and/or increase our borrowing costs, which may adversely affect our operations and financial results.
This could result in the delay, reduction or termination of our research, which could harm our business. We have incurred in the past and may in the future incur substantial indebtedness that may decrease our business flexibility, access to capital, and/or increase our borrowing costs, which may adversely affect our operations and financial results.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to loss of customers; inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to loss of customers; inability to process personal data or to operate in certain jurisdictions; interruptions or stoppages in our business operations (including clinical trials); limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations.
Thus, we are not able to promote any products we develop for indications or uses for which they are not approved. Additionally, in the EU, it is prohibited to promote prescription drugs to the general public and we are therefore limited to promote our products exclusively to healthcare professionals.
Thus, we are not able to promote any products we develop for indications or uses for which they are not approved. Additionally, in the EU, it is prohibited to promote prescription drugs to the general public and we are therefore limited to promote our products exclusively to healthcare professionals, which is also subject to restrictions.
Moreover, with respect to certain biologics and gene therapies, there may be some uncertainty regarding how similarity between product candidates designed to treat the same rare disease or condition may affect such product candidates’ orphan drug regulatory exclusivities.
Moreover, with respect to certain biologics, there may be some uncertainty regarding how similarity between product candidates designed to treat the same rare disease or condition may affect such product candidates’ orphan drug regulatory exclusivities.
As of December 31, 2024, we had $600.0 million (undiscounted) principal amount of indebtedness, all of which was outstanding under the 2027 Notes.
As of December 31, 2025, we had $600.0 million (undiscounted) principal amount of indebtedness, all of which was outstanding under the 2027 Notes.
Remote work has also increased risks to our information technology systems and data, as our employees utilize network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations.
Remote work poses increased risks to our information technology systems and data, as our employees utilize network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations.
International operations inherently subject us to a number of risks and uncertainties, including: • the increased complexity and costs inherent in managing international operations; • diverse regulatory and compliance requirements, and changes in those requirements that could restrict our ability to manufacture, market and sell our products; • geopolitical and economic instability, such as the instability caused by Russia’s invasion of Ukraine and the conflicts in the Middle East; • diminished protection of intellectual property in some countries outside of the U.S.; • trade protection measures and import or export licensing requirements; • difficulty in staffing and managing international operations; • differing labor regulations and business practices; • parallel trade in our products, such as importation of our products, whether legally or illegally, from countries where our products are sold at lower prices into countries where the products are sold at higher prices; • potentially negative consequences from changes in or interpretations of tax laws; • changes in international medical reimbursement policies and programs; • financial risks such as longer payment cycles, difficulty collecting accounts receivable, exposure to fluctuations in foreign currency exchange rates and potential currency controls imposed by non-U.S. governments; • regulatory and compliance risks that relate to maintaining accurate information and control over sales and distributors’ and service providers’ activities that may fall within the purview of the Foreign Corrupt Practices Act (the FCPA); and • rapidly evolving global laws and regulations relating to data protection and the privacy and security of commercial and personal information.
International operations inherently subject us to a number of risks and uncertainties, including: • the increased complexity and costs inherent in managing international operations; • diverse regulatory and compliance requirements, and changes in those requirements that could restrict our ability to manufacture, market and sell our products; • geopolitical and economic instability; • diminished protection of intellectual property in some countries outside of the U.S.; • impact of new or increased tariffs, other trade protection measures (such as import or export licensing requirements), and escalating trade tensions; 44 • difficulty in staffing and managing international operations; • differing labor regulations and business practices; • parallel trade in our products, such as importation or our products, whether legally or illegally, from countries where our products are sold at lower prices into countries where the products are sold at higher prices; • potentially negative consequences from changes in or interpretations of tax laws; • changes in international medical reimbursement policies and programs; • financial risks such as longer payment cycles, difficulty collecting accounts receivable, exposure to fluctuations in foreign currency exchange rates and potential currency controls imposed by non-U.S. governments; • regulatory and compliance risks that relate to maintaining accurate information and control over sales and distributors’ and service providers’ activities that may fall within the purview of the Foreign Corrupt Practices Act (the FCPA); and • rapidly evolving global laws and regulations relating to data protection and the privacy and security of commercial and personal information.
Any such situation could adversely affect our business, financial condition, and results of operations. Activist investor actions threatened or commenced against us have and could in the future cause us to incur substantial costs, divert management's attention and resources, cause uncertainty about the strategic direction of our business and adversely affect our business, financial position and results of operations.
Activist investor actions threatened or commenced against us have and could in the future cause us to incur substantial costs, divert management's attention and resources, cause uncertainty about the strategic direction of our business and adversely affect our business, financial position and results of operations.
Regulators in the United States are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.
Regulators across the world are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.
The IRA's provisions began taking effect progressively starting in 2023, although they may be subject to legal challenges. Thus, while it is unclear how the IRA will be implemented, it will likely have a significant impact on the pharmaceutical industry.
The IRA's provisions began taking effect progressively starting in 2023, although they may be subject to legal challenges. Thus, while it is unclear how the IRA will be implemented, it will likely have a significant impact on the pharmaceutical industry. In addition, the current U.S.
For biologics and gene therapies, the FDA’s determination of whether a drug is the same drug or a different drug will be based on the principal molecular structural features of the products.
For biologics, the FDA’s determination of whether a drug is the same drug or a different drug will be based on the principal molecular structural features of the products.
If we default under the 2024 Credit Agreement, the outstanding borrowings thereunder could become immediately due and payable, the 2024 Credit Facility lenders could refuse to permit additional borrowings under the facility, or it could lead to defaults under agreements governing our current or future indebtedness, including the indenture governing the 2027 Notes.
If we default under the 2024 Credit Agreement or the indentures governing our Notes, the outstanding borrowings thereunder could become immediately due and payable, the 2024 Credit Facility lenders could refuse to permit additional borrowings under the facility, or it could lead to defaults under agreements governing our current or future indebtedness, including the 2024 Credit Agreement and the indentures governing the Notes, as applicable.
Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties with whom we work.
Any of the previously identified or similar threats have in the past and may in the future cause a security incident or other interruption that have in the past and may in the future result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties with whom we work.
Prior to the IRA, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the PPACA), expanded healthcare coverage within the U.S., primarily through the imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program.
For example, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the PPACA), expanded healthcare coverage within the U.S., primarily through the imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program.
If we are unable to successfully execute our strategy, our business, financial condition and results of operations may be materially and adversely affected. As part of the strategy, we have announced that we are advancing VOXZOGO for the treatment of conditions beyond achondroplasia, including hypochondroplasia, idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency.
If we are unable to successfully execute our strategy, our business, financial condition and results of operations may be materially and adversely affected. As part of the strategy, we are continuing to advance VOXZOGO for the treatment of conditions beyond achondroplasia, including hypochondroplasia, idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency.
In addition, individual states in the U.S. have also increasingly enacted laws and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, price and price increase disclosure and reporting requirements, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
At the U.S. state level, legislatures have also increasingly enacted laws and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, price and price increase disclosure and reporting requirements, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
If the related medicinal product has been, or is in the process of being, authorized through the centralized procedure for the authorization of medicinal products, the Notified Body will, before it can issue a CE Certificate of Conformity, be required to seek a scientific opinion from the EMA on the suitability of the companion diagnostic for use in relation to the medicinal product concerned.
If the related medicinal product has been, or is in the process of being, authorized through the centralized procedure for the authorization of medicinal products, the Notified Body will, before it can issue the relevant EU technical documentation assessment certificate, be required to seek a scientific opinion from the EMA on the suitability of the companion diagnostic for use in relation to the medicinal product concerned.
The market price of our common stock has fluctuated, and in the future could fluctuate, due to factors including: • product sales and profitability of our products; • manufacturing, supply or distribution of our product candidates and products; • progress of our product candidates through the regulatory process and our ability to successfully commercialize any such products that receive regulatory approval; • results of clinical trials, announcements of technological innovations or new products by us or our competitors; • generic competition to KUVAN tablets and powder described above in this Risk Factors section or potential generic competition from future competitors; • government regulatory action affecting our product candidates, our products or our competitors’ product candidates and products in both the U.S. and non-U.S. countries; • developments or disputes concerning patent or proprietary rights; • general market conditions and fluctuations for the emerging growth and pharmaceutical market sectors; 45 • economic conditions in the U.S. or abroad; • negative publicity about us or the pharmaceutical industry; • changes in the structure of healthcare payment systems; • cybersecurity incidents experienced by us or others in our industry; • broad market fluctuations in the U.S., the EU or in other parts of the world; • actual or anticipated fluctuations in our operating results, including due to timing of large periodic orders for our products by governments in certain countries; • changes in company assessments or financial estimates by securities analysts; • certain actions by activist investors that may be threatened or commenced against us; • acquisitions of products, businesses, or other assets; • industry, financial analyst, or investor reaction to public announcements by us or our competitors; and • sales of our shares of stock by us, our significant stockholders, or members of our management or Board of Directors.
The market price of our common stock has fluctuated, and in the future could fluctuate, due to factors including: • product sales and profitability of our products; • manufacturing, supply or distribution of our product candidates and products; • progress of our product candidates through the regulatory process and our ability to successfully commercialize any such products that receive regulatory approval; • results of clinical trials, announcements of technological innovations or new products by us or our competitors; • strategic transactions, including acquisition of products, businesses, or other assets; • generic competition from current and future competitors; • government regulatory action affecting our product candidates, our products or our competitors’ product candidates and products in both the U.S. and non-U.S. countries; • developments or disputes concerning patent or proprietary rights; • general market conditions and fluctuations for the emerging growth and pharmaceutical market sectors; • economic conditions in the U.S. or abroad; • negative publicity about us or the pharmaceutical industry; • changes in the structure of healthcare payment systems; • cybersecurity incidents experienced by us or others in our industry; • broad market fluctuations in the U.S., the EU or in other parts of the world; • the impact of new or increased tariffs and escalating trade tensions; • actual or anticipated fluctuations in our operating results, including due to timing of large periodic orders for our products by governments in certain countries; • changes in company assessments or financial estimates by securities analysts; • certain actions by activist investors that may be threatened or commenced against us; • industry, financial analyst, or investor reaction to public announcements by us or our competitors; and • sales of our shares of stock by us, our significant stockholders, or members of our management or Board of Directors.
Numerous factors could cause interruptions in the supply or manufacture of our products and product candidates, including: • timing, scheduling and prioritization of production by our contract manufacturers or a breach of our agreements by our contract manufacturers; • labor interruptions; • changes in our sources for manufacturing; 39 • the timing and delivery of shipments; • our failure to locate and obtain replacement suppliers and manufacturers as needed on a timely basis; and • conditions affecting the cost and availability of raw materials, including inflation.
Numerous factors could cause interruptions in the supply or manufacture of our products and product candidates, including: • timing, scheduling and prioritization of production by our contract manufacturers or a breach of our agreements by our contract manufacturers; • labor interruptions; • changes in our sources for manufacturing; • the timing and delivery of shipments; • our failure to locate and obtain replacement suppliers and manufacturers as needed on a timely basis; • geopolitical instability resulting from war, terrorism and other violence; and • conditions affecting the cost and availability of raw materials, including inflation.
VOXZOGO addresses larger patient populations than most of our other products, and product candidates that we are currently developing or may license or acquire in the future may be intended for similarly larger patient populations than we have historically targeted.
VOXZOGO addresses larger patient populations than most of our other products, and product candidates that we are currently developing or may license or acquire in the future may be intended for similarly larger patient populations than we have historically targeted. We are also expanding our pipeline through external innovation.
Our outstanding indebtedness consists of the 2027 Notes, which, if not converted, will be required to be repaid in cash at maturity in May 2027.
Our outstanding indebtedness consists of the 2027 Notes, which, if not converted, will be required to be repaid in cash at maturity in May 2027, and the 2034 Notes, which are required to be repaid in cash at maturity in February 2034.
In the EU, materials we submit to the EMA in connection with our clinical trials that were traditionally regarded as confidential, proprietary information, such as study protocols, information regarding manufacturing methods and controls, and intermediate data analyses, are now subject to public disclosure. Moreover, clinical trial data submitted to the EMA in our MAAs are also available to the public.
In the EU, materials we submit to the EMA in connection with our clinical trials that were traditionally regarded as confidential, proprietary information, such as study protocols, information regarding manufacturing methods and controls, and 48 intermediate data analyses, are now subject to public disclosure.
Various macroeconomic factors could adversely affect our business and the results of our operations and financial condition, including changes in inflation, interest rates, or foreign currency exchange rates, natural disasters, geopolitical instability resulting from war, terrorism and other violence, such as the instability caused by Russia's invasion of Ukraine and the conflicts in the Middle East, tariffs and trade tensions, effects of potential global public health threats and overall economic conditions and uncertainties, including those resulting from the current and future conditions in the global financial markets and volatility and disruptions in the equity and debt markets.
Various macroeconomic factors could adversely affect our business and the results of our operations and financial condition, including changes in inflation, interest rates, or foreign currency exchange rates, natural disasters, geopolitical instability resulting from war, terrorism and other violence, tariffs and escalating trade tensions, effects of potential global public health threats and overall economic conditions and uncertainties, including those resulting from the current and future conditions in the global financial markets and volatility and disruptions in the equity and debt markets.
In August 2024, we entered into an unsecured credit agreement (the 2024 Credit Agreement) with Citibank, N.A., as the administrative agent, and the other lenders party thereto, providing for $600.0 million in revolving loan 37 commitments (the 2024 Credit Facility). The 2024 Credit Facility matures in August 2029.
In August 2024, we entered into an unsecured credit agreement (the 2024 Credit Agreement) with Citibank, N.A., as the administrative agent, and the other lenders party thereto, providing for $600.0 million in revolving loan commitments (the 2024 Credit Facility). The 2024 Credit Facility matures in August 2029. Additionally, in February 2026, we issued the 2034 Notes.
For example, the OECD, which represents a coalition of member countries including the U.S. and other countries in which we have operations, is working on proposals, commonly referred to as “BEPS 2.0”, which, to the extent implemented, would make important changes to the international tax system.
For example, the OECD, which represents a coalition of member countries including the U.S. and other countries in which we have operations, is working on the implementation of proposals, commonly referred to as “BEPS 2.0”, which have made (and are expected to continue to make) important changes to the international tax system.
In 2024, we announced our new corporate strategy for focused on innovation, growth, and value commitment, which includes, among other things, the acceleration or discontinuation of certain programs, the expansion of our pipeline, update to our commercial organizational model, and cost transformation.
We continue to pursue the corporate strategy we announced in 2024, which is focused on innovation, growth, and value commitment, which includes, among other things, the acceleration or discontinuation of certain programs, the continued expansion of our pipeline, updates to our commercial organizational model, and cost transformation.
If the USD were to weaken against another currency, assuming all other variables remained constant, our revenues would increase, having a positive impact on earnings, and our overall expenses would increase, having a negative impact on earnings.
If the USD were to weaken against another currency (as has been the case against the Euro in 2025), assuming all other variables remained constant, our revenues would increase, having a positive impact on earnings, and our overall expenses would increase, having a negative impact on earnings.
Our products have received regulatory approval to be commercially marketed and sold in the U.S., the EU, and certain other countries except ROCTAVIAN, which has received regulatory approval to be commercially marketed in the U.S. and conditional approval to be commercially marketed in the EU.
Our marketed products have received regulatory approval to be commercially marketed and sold in the U.S., the EU, and certain other countries.
Our valuation and stock price may have no meaningful relationship to current or historical earnings, asset values, book value or many other criteria based on conventional measures of stock value.
Our stock price has been and may in the future be volatile. Our valuation and stock price may have no meaningful relationship to current or historical earnings, asset values, book value or many other criteria based on conventional measures of stock value.
The anti-corruption and anti-bribery laws to which we are subject generally prohibit companies and their intermediaries from making improper payments to non-U.S. government officials or other persons for the purposes of influencing official decisions or obtaining or retaining business and/or other benefits.
The anti-corruption and anti-bribery laws to which we are subject generally prohibit individuals, entities, and their intermediaries from directly or indirectly making, offering, providing, promising, or authorizing provision of improper payments to non-U.S. government officials or other persons for the purposes of influencing official decisions or obtaining or retaining business and/or other benefits.
Our products approved under BLAs in the U.S. or as a result of Marketing Authorization Applications (MAAs) in the EU, as well as our product candidates that may be approved in the future, could be reference products for biosimilar marketing applications.
Our products approved under BLAs in the U.S., Marketing Authorization Applications (MAAs) in the EU, or comparable regulatory approval applications in other countries, as well as our product candidates that may be approved in the future, could be reference products for biosimilar marketing applications.
Changes in funding for the FDA, the EMA, other comparable regulatory authorities and other government agencies or government shutdowns could hinder the ability of such authorities and agencies to hire and retain key leadership and other personnel or otherwise prevent those authorities and agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.
Disruptions at the FDA, the EMA, other comparable regulatory authorities and other government agencies, including a reduction in some agencies' workforces and/or inadequate funding, could hinder the ability of such authorities and agencies to hire and retain key leadership and other personnel or otherwise prevent those authorities and agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.
As a result, we could face employee attrition beyond our intended reductions in force and adverse effects on employee morale, diversion of management attention, and adverse effects to our reputation as an employer, which could make it more difficult for us to hire employees in the future.
We have in the past and may in the future announce reductions in our global workforce, which could lead to employee attrition beyond our intended reductions in force and adverse effects on employee morale, diversion of management attention, and adverse effects to our reputation as an employer, which could in turn make it more difficult for us to hire employees in the future.
Additionally, companies that transfer personal data to recipients outside of the EEA and/or UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators individual litigants and activist groups.
Additionally, companies that transfer personal data to recipients outside of the EEA and/or UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators individual litigants and activist groups. Additionally, the U.S. Department of Justice issued a rule entitled the Preventing Access to U.S.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThe Board and the Audit Committee receive periodic reports, summaries, and presentations from our senior management, including the Chief Information Officer and Global Head of Cybersecurity, concerning our significant cybersecurity threats and risk and the processes the Company has implemented to address them. 55 We have an Executive Cybersecurity Committee (ECC), which is comprised of our Chief Financial Officer (CFO), Chief Information Officer, Chief Legal Officer, Chief Accounting Officer, and Global Head of Cybersecurity, with the goal of providing oversight of the Company’s cybersecurity program.
Biggest changeWe have an Executive Cybersecurity Committee (ECC), which is comprised of our Chief Financial Officer (CFO), Chief Digital and Information Officer, Chief Legal Officer and Chief Accounting Officer, with the goal of providing oversight of the Company’s cybersecurity program.
The ECC is responsible for, among other things, evaluating and determining the materiality of cybersecurity incidents as well as reviewing and approving any public disclosures with respect to material cybersecurity incidents.
The ECC is responsible for, among other things, evaluating and determining the materiality of 60 cybersecurity incidents as well as reviewing and approving any public disclosures with respect to material cybersecurity incidents.
Our cybersecurity incident response policy is designed for our cybersecurity operations team, which is led by our Global Head of Cybersecurity, who works in conjunction with the cross-functional incident response team, to escalate certain cybersecurity incidents to the ECC depending on the circumstances. The ECC also has the responsibility of reporting to the Board and/or the Audit Committee.
Our cybersecurity incident response policy is designed for our cybersecurity operations team, which is led by our Chief Digital and Information Officer, who works in conjunction with the cross-functional incident response team, to escalate certain cybersecurity incidents to the ECC depending on the circumstances. The ECC also has the responsibility of reporting to the Board and/or the Audit Committee.
We maintain a Cybersecurity Risk Committee (CRC) that is comprised of management level representatives from key organizations and functions within the Company and led by our Global Head of Cybersecurity.
We maintain a Cybersecurity Risk Committee (CRC) that is comprised of management level representatives from key organizations and functions within the Company and led by our Chief Digital and Information Officer.
Our cybersecurity risk assessment and management processes are implemented and maintained by certain members of Company management, including the Chief Information Officer, who reports to the CFO. Our Chief Information Officer has nearly 25 years of industry experience and has been with us since 2008.
Our cybersecurity risk assessment and management processes are implemented and maintained by certain members of Company management, including the Chief Digital and Information Officer, who reports to the CEO. Our Chief Digital and Information Officer joined us in January 2026, and has more than 20 years of experience in information technology and artificial intelligence in the biopharmaceutical industry.
Removed
While we have not, as of the date of this Annual Report on Form 10-K, experienced a cybersecurity incident that resulted in a material adverse impact to our business or operations, there can be no guarantee that we will not experience such an incident in the future.
Added
The Board and the Audit Committee receive periodic reports, summaries, and presentations from our senior management concerning our significant cybersecurity threats and risk and the processes the Company has implemented to address them.
Removed
Our Global Head of Cybersecurity has over 20 years of cybersecurity and privacy experience, including serving in similar roles leading and overseeing cybersecurity programs at public companies.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeProperties The following table contains information about our significant owned and leased properties as of December 31, 2024: Location Approximate Square Feet Use Lease Expiration Date San Rafael facility, San Rafael, California 407,300 Corporate headquarters, laboratory and office Owned property Several facilities in Novato, California 293,300 Clinical and commercial manufacturing, laboratory and office Owned property Several leased facilities in Novato, California 158,600 Office and warehouse 2027 Shanbally facility, Cork, Ireland 260,700 Manufacturing, laboratory and office Owned property We expect that these properties, together with our other smaller leased office facilities in various countries, will be adequate for our operations for the foreseeable future.
Biggest changeProperties The following table contains information about our significant owned and leased properties as of December 31, 2025: Location Approximate Square Feet Use Lease Expiration Date San Rafael facility, San Rafael, California 407,200 Corporate headquarters, laboratory and office Owned property Several facilities in Novato, California 292,300 Clinical and commercial manufacturing, laboratory and office Owned property Several leased facilities in Novato, California 149,500 Office and warehouse 2027 Shanbally facility, Cork, Ireland 260,700 Manufacturing, laboratory and office Owned property We expect that these properties, together with our other smaller leased office facilities in various countries, will be adequate for our operations for the foreseeable future.
Added
Item 3. Legal Proceedings None. Item 4. Mine Safety Disclosures Not applicable. 61 Table of Contents Part II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

2 edited+0 added−0 removed3 unchanged
Biggest changeThe comparisons shown in the graph are based upon historical data and we caution that the stock price performance shown in the graph is not indicative of, nor intended to forecast, the potential future performance of our stock. * $100 invested on December 31, 2019 in stock or index, including reinvestment of dividends 2019 2020 2021 2022 2023 2024 BioMarin Pharmaceutical Inc. $ 100.00 $ 103.71 $ 104.49 $ 122.40 $ 114.04 $ 77.74 Nasdaq Composite Index $ 100.00 $ 144.92 $ 177.06 $ 119.45 $ 172.77 $ 223.87 Nasdaq Biotechnology $ 100.00 $ 126.42 $ 126.45 $ 113.65 $ 118.87 $ 118.20 SPDR S&P Biotech ETF $ 100.00 $ 148.33 $ 118.00 $ 87.48 $ 94.12 $ 95.07 59 Table of Contents Item 6. [Reserved] 60
Biggest changeThe comparisons shown in the graph are based upon historical data and we caution that the stock price performance shown in the graph is not indicative of, nor intended to forecast, the potential future performance of our stock. * $100 invested on December 31, 2020 in stock or index, including reinvestment of dividends 2020 2021 2022 2023 2024 2025 BioMarin Pharmaceutical Inc. $ 100.00 $ 100.75 $ 118.02 $ 109.96 $ 74.96 $ 67.77 Nasdaq Composite Index $ 100.00 $ 122.18 $ 82.43 $ 119.22 $ 154.48 $ 187.14 Nasdaq Biotechnology $ 100.00 $ 100.02 $ 89.90 $ 94.03 $ 93.49 $ 124.75 SPDR S&P Biotech ETF $ 100.00 $ 79.55 $ 58.97 $ 63.45 $ 64.09 $ 87.10 Item 6. [Reserved] 63
Holders As of February 18, 2025, there were 34 holders of record of 190,777,052 outstanding shares of our common stock. 58 Table of Contents Performance Graph The following is not deemed “filed” with the Securities and Exchange Commission and is not to be incorporated by reference into any filing we make under the Securities Act of 1933, as amended, whether made before or after the date hereof and irrespective of any general incorporation by reference language in such filing.
Holders As of February 19, 2026, there were 28 holders of record of 192,323,359 outstanding shares of our common stock. 62 Table of Contents Performance Graph The following is not deemed “filed” with the Securities and Exchange Commission and is not to be incorporated by reference into any filing we make under the Securities Act of 1933, as amended, whether made before or after the date hereof and irrespective of any general incorporation by reference language in such filing.

Item 7. Management's Discussion & Analysis

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

58 edited+38 added−16 removed33 unchanged
Biggest changeDollars, except as otherwise disclosed) • NAGLAZYME: higher sales volume due to timing of orders in countries that place large government orders, particularly in the Middle East; • ALDURAZYME: higher sales volume due to timing of order fulfillment to Sanofi as we recognize ALDURAZYME revenues when the product is released and control is transferred to Sanofi; • PALYNZIQ: higher sales volume from new patients initiating therapy, primarily in the U.S.; • VIMIZIM: higher sales volume due to new patients initiating therapy in the U.S. and timing of orders in countries that place large government orders, particularly in Europe; and • ROCTAVIAN: higher sales volume from new patients treated in the U.S. and Europe.
Biggest changeThe increase in Net Product Revenues in 2025 as compared to 2024 was primarily attributed to the following: • VOXZOGO: higher sales volume from new patients initiating therapy across all regions; • PALYNZIQ: higher sales volume from new patients initiating therapy, primarily in the U.S.; • VIMIZIM: higher sales volume due to timing of orders in countries that place large government orders, primarily from countries in the Middle East and Latin America; • ALDURAZYME: higher sales volume due to timing of order fulfillment to Sanofi as we recognize ALDURAZYME revenues when the product is released and control is transferred to Sanofi; and • BRINEURA: higher sales volume from new patients initiating therapy, primarily in the U.S. and Latin America.
MD&A is provided as a supplement to, and should be read in conjunction with, our audited Consolidated Financial Statements and the accompanying notes to the Consolidated Financial Statements and other disclosures included in this Annual Report on Form 10-K, including the disclosures under “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K.
The MD&A is provided as a supplement to, and should be read in conjunction with, our audited Consolidated Financial Statements and the accompanying notes to the Consolidated Financial Statements and other disclosures included in this Annual Report on Form 10-K, including the disclosures under “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K.
Recent Accounting Pronouncements See Note 1 to our accompanying Consolidated Financial Statements for a full description of recent accounting pronouncements and our expectation of their impact on our results of operations and financial condition. 70 Table of Contents
Recent Accounting Pronouncements See Note 1 to our accompanying Consolidated Financial Statements for a full description of recent accounting pronouncements and our expectation of their impact on our results of operations and financial condition. 74 Table of Contents
We group all of our R&D activities and related expense into three categories: (i) Research and early pipeline, (ii) Later-stage clinical programs and (iii) Marketed products as follows: Category Description Research and early pipeline R&D expense incurred in activities substantially in support of early research through the completion of phase 2 clinical trials, including drug discovery, toxicology, pharmacokinetics and drug metabolism and process development.
Dollars, except as otherwise disclosed) We group all of our R&D activities and related expense into three categories: (i) Research and early pipeline, (ii) Later-stage clinical programs and (iii) Marketed products as follows: Category Description Research and early pipeline R&D expense incurred in activities substantially in support of early research through the completion of phase 2 clinical trials, including drug discovery, toxicology, pharmacokinetics and drug metabolism and process development.
We believe that the combination of our internal research programs and partnerships will allow us to continue to develop and commercialize innovative therapies for people with serious and life-threatening rare diseases and medical conditions.
We believe that the combination of our internal research programs and partnerships and acquisitions of external assets will allow us to continue to develop and commercialize innovative therapies for people with serious and life-threatening rare diseases and medical conditions.
We continuously evaluate the recoverability of costs associated with pre-launch or pre-qualification manufacturing activities, if any, and capitalize the costs incurred related to those activities if we determine that recoverability is highly likely and therefore future revenues are expected.
We continuously evaluate the recoverability of costs associated with pre-launch or pre-qualification manufacturing activities, if any, and capitalize the costs incurred related to those activities if we determine that recoverability is probable and therefore future revenues are expected.
We establish liabilities or reduce assets for certain tax positions when we believe those certain tax positions are not more likely than not to be sustained if challenged. Each quarter, we evaluate these uncertain tax positions and adjust the related tax assets and liabilities in light of changing facts and circumstances.
Dollars, except as otherwise disclosed) We establish liabilities or reduce assets for certain tax positions when we believe those certain tax positions are not more likely than not to be sustained if challenged. Each quarter, we evaluate these uncertain tax positions and adjust the related tax assets and liabilities in light of changing facts and circumstances.
Dollars, except as otherwise disclosed) Cost of Sales and Gross Margin Cost of Sales includes raw materials, personnel, facility and other costs associated with manufacturing our commercial products. These costs include production materials, production costs at our manufacturing facilities, third-party manufacturing costs, amortization of technology transfer intangible assets and internal and external final formulation and packaging costs.
Cost of Sales and Gross Margin Cost of Sales includes raw materials, personnel, facility and other costs associated with manufacturing our commercial products. These costs include production materials, production costs at our manufacturing facilities, third-party manufacturing costs, amortization of technology transfer intangible assets and internal and external final formulation and packaging costs.
Dollars, except as otherwise disclosed) Gross-to-Net Sales Adjustments – We record product sales net of estimated mandatory and supplemental discounts to government payers, discounts to private payers and other related charges. Rebates, cash discounts and distributor fees represent the majority of our gross-to-net deductions and are recorded in the same period the related sales occur.
Gross-to-Net Sales Adjustments – We record product sales net of estimated mandatory and supplemental discounts to government payers, discounts to private payers and other related charges. Rebates, cash discounts and distributor fees represent the majority of our gross-to-net deductions and are recorded in the same period the related sales occur.
Dollars, except as otherwise disclosed) Uncertainty Relating to Macroeconomic Environment Conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange rates, natural disasters, geopolitical instability, tariffs and tensions, and supply chain disruptions, could impact our global revenue sources and our overall business operations.
Dollars, except as otherwise disclosed) Uncertainty Relating to Macroeconomic Environment Conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange rates, natural disasters, geopolitical instability, impact of new or increased tariffs and escalating trade tensions, regulatory uncertainty, and supply chain disruptions, could impact our global revenue sources and our overall business operations.
The following table summarizes the consolidated activities and ending balances of all our gross-to-net sales adjustments: Balance at Beginning of Year Provision for Current Period Sales Payments Balance at End of Year Year ended December 31, 2024 $ 152.1 $ 435.1 $ (392.2) $ 195.0 Year ended December 31, 2023 $ 115.0 $ 370.7 $ (333.6) $ 152.1 Year ended December 31, 2022 $ 85.6 $ 282.5 $ (253.1) $ 115.0 Income Taxes We calculate and provide for income taxes in each of the tax jurisdictions in which we operate.
The following table summarizes the consolidated activities and ending balances of all our gross-to-net sales adjustments: Balance at Beginning of Year Provision for Current Period Sales Payments Balance at End of Year Year ended December 31, 2025 $ 195.0 $ 487.8 $ (436.7) $ 246.1 Year ended December 31, 2024 $ 152.1 $ 435.1 $ (392.2) $ 195.0 Year ended December 31, 2023 $ 115.0 $ 370.7 $ (333.6) $ 152.1 Income Taxes We calculate and provide for income taxes in each of the tax jurisdictions in which we operate.
Cost of Sales also includes royalties payable to third parties based on sales of our products, idle plant costs and charges for inventory valuation reserves.
Cost of Sales also includes royalties payable to third parties based on sales of our products, idle plant costs and charges for inventory write downs.
A summary of our commercial products, as of December 31, 2024, is provided below: Commercial Products Indication VIMIZIM (elosulfase alpha) Mucopolysaccharidosis (MPS) IVA VOXZOGO (vosoritide) Achondroplasia NAGLAZYME (galsulfase) MPS VI PALYNZIQ (pegvaliase-pqpz) Phenylketonuria (PKU) ALDURAZYME (laronidase) MPS I BRINEURA (cerliponase alfa) Neuronal ceroid lipofuscinosis type 2 (CLN2) KUVAN (sapropterin dihydrochloride) PKU ROCTAVIAN (valoctocogene roxaparvovec) Severe Hemophilia A 2024 Financial Highlights Key components of our results of operations include the following: Twelve Months Ended December 31, 2024 2023 2022 Total revenues $ 2,853.9 $ 2,419.2 $ 2,096.0 Cost of sales $ 580.2 $ 532.1 $ 503.0 Research and development (R&D) $ 747.2 $ 746.8 $ 649.6 Selling, general and administrative (SG&A) $ 1,009.0 $ 892.4 $ 823.2 Net income $ 426.9 $ 167.6 $ 141.6 See “Results of Operations” below for discussion of our results for the periods presented. 61 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
A summary of our commercial products, as of December 31, 2025, is provided below: Commercial Products Indication VOXZOGO (vosoritide) Achondroplasia Enzyme Therapies: VIMIZIM (elosulfase alpha) Mucopolysaccharidosis (MPS) IVA NAGLAZYME (galsulfase) MPS VI PALYNZIQ (pegvaliase-pqpz) Phenylketonuria (PKU) ALDURAZYME (laronidase) MPS I BRINEURA (cerliponase alfa) Neuronal ceroid lipofuscinosis type 2 (CLN2) KUVAN (sapropterin dihydrochloride) PKU ROCTAVIAN (valoctocogene roxaparvovec) Severe Hemophilia A 2025 Financial Highlights Key components of our results of operations include the following: Twelve Months Ended December 31, 2025 2024 2023 Total revenues $ 3,221.3 $ 2,853.9 $ 2,419.2 Cost of sales $ 717.4 $ 580.2 $ 532.1 Research and development (R&D) $ 921.9 $ 747.2 $ 746.8 Selling, general and administrative (SG&A) $ 1,153.0 $ 1,009.0 $ 892.4 Provision for income taxes $ 133.6 $ 114.9 $ 20.9 Net income $ 348.9 $ 426.9 $ 167.6 See “Results of Operations” below for discussion of our results for the periods presented. 64 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
For example, we may require additional financing to fund the repayment of our convertible debt due in 2027, future milestone payments and our future operations, including the commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and acquisitions.
For example, we may require additional financing to fund the repayment of our outstanding indebtedness, future milestone payments and our future operations, including the commercialization of our products and product candidates currently under development, preclinical studies and clinical trials, and potential licenses and acquisitions.
See “Quantitative and Qualitative Disclosures about Market Risk” in Part II, Item 7A of this Annual Report on Form 10-K and the risk factor “Our international operations pose currency risks, which may adversely affect our operating results and net income” in “Risk Factors” included in Part I, Item 1A of this Annual Report for information on currency exchange rate risk related to our Net Product Revenues. 63 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
See “Quantitative and Qualitative Disclosures about Market Risk” in Part II, Item 7A of this Annual Report on Form 10-K and the risk factor “Our international operations pose currency risks, which may adversely affect our operating results and net income” in “Risk Factors” included in Part I, Item 1A of this Annual Report for information on currency exchange rate risk related to our Net Product Revenues.
Results of Operations 2023 Compared to 2022 For a discussion of our results of operations pertaining to 2023 as compared to 2022 see Item 7 , "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the year ended December 31, 2023 (filed with the Securities and Exchange Commission (SEC) on February 26, 2024). 67 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Results of Operations 2024 Compared to 2023 For a discussion of our results of operations pertaining to 2024 as compared to 2023 see Item 7 , "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the year ended December 31, 2024 (filed with the Securities and Exchange Commission (SEC) on February 24, 2025).
Critical Accounting Estimates In preparing our Consolidated Financial Statements in accordance with U.S. GAAP and pursuant to the rules and regulations promulgated by the SEC, we make assumptions, judgments and estimates that can have a significant impact on our net income/loss and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures.
GAAP and pursuant to the rules and regulations promulgated by the SEC, we make assumptions, judgments and estimates that can have a significant impact on our net income/loss and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures.
The credit facility matures in August 2029. As of December 31, 2024 there were no amounts outstanding under the credit facility and we were in compliance with all covenants. See Note 10 to our accompanying Consolidated Financial Statements for additional discussion on our convertible debt and credit facility.
As of December 31, 2025 there were no amounts outstanding under the Revolving Facility and we were in compliance with all covenants. The New Revolving Facility is expected to replace the existing Revolving Facility. See Note 10 to our accompanying Consolidated Financial Statements for additional discussion on our convertible debt and credit facility.
Dollars, except as otherwise disclosed) Intangible Asset Amortization and Gain on Sale of Nonfinancial Assets Changes during the periods presented for Intangible Asset Amortization and Gain on Sale of Nonfinancial Assets were as follows: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Amortization of intangible assets $ 43.3 $ 62.2 $ 62.8 $ (18.9) $ (0.6) Changes in the fair value of contingent consideration — — 4.4 — (4.4) Total intangible asset amortization and contingent consideration $ 43.3 $ 62.2 $ 67.2 $ (18.9) $ (5.0) Gain on sale of nonfinancial assets $ 10.0 $ — $ 108.0 $ 10.0 $ (108.0) Amortization of intangible assets : the decrease in expense for 2024 as compared to 2023 was due to the increase in the estimated useful life of an intangible asset as a result of the extension of a patent and an intangible asset becoming fully amortized during the fourth quarter of 2023.
Intangible Asset Amortization and Gain on Sale of Nonfinancial Assets Changes during the periods presented for Intangible Asset Amortization and Gain on Sale of Nonfinancial Assets were as follows: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Amortization of intangible assets $ 19.4 $ 43.3 $ 62.2 $ (23.9) $ (18.9) Gain on sale of nonfinancial assets $ — $ 10.0 $ — $ (10.0) $ 10.0 Amortization of intangible assets : the decrease in amortization expense for 2025 as compared to 2024 was due to the increase in the estimated useful life of an intangible asset as a result of the extension of a patent during the second half of 2024 and an intangible asset becoming fully amortized during the fourth quarter of 2024.
Certain countries in which we have operations, including Ireland, have adopted Pillar Two rules, recently released from the Organisation for Economic Co-operation and Development (OECD), including a minimum tax rate of 15%. It is uncertain whether the United States will enact legislation to adopt the Pillar Two framework.
Certain countries in which we have operations, including Ireland, have adopted Pillar Two framework, recently released from the Organisation for Economic Co-operation and Development (OECD), including a minimum tax rate of 15%. The U.S. has not enacted legislation to adopt the Pillar Two framework.
Material Cash Requirements Purchase and Lease Obligations As of December 31, 2024, we had purchase obligations of approximately $641.9 million, of which $482.0 million is expected to be paid in 2025.
Material Cash Requirements Purchase and Lease Obligations As of December 31, 2025, we had purchase obligations of approximately $590.8 million, of which $354.1 million is expected to be paid in 2026.
We are mindful that conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange rates, natural disasters, geopolitical instability, tariffs and trade tensions, and supply chain disruptions could affect our ability to achieve our goals. In addition, we sell our products in certain countries that face economic volatility and weakness.
We are mindful that conditions in the current macroeconomic environment, such as inflation, changes in interest and foreign currency exchange rates, natural disasters, geopolitical instability, impact of new or increased tariffs and escalating trade tensions, regulatory uncertainty, and supply chain disruptions could affect our ability to achieve our goals.
The following table shows our Net Product Revenues denominated in USD and foreign currencies: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Sales denominated in USD $ 1,366.0 $ 1,137.8 $ 1,008.8 $ 228.2 $ 129.0 Sales denominated in foreign currencies 1,443.4 1,234.7 1,033.2 208.7 201.5 Total net product revenues $ 2,809.4 $ 2,372.5 $ 2,042.0 $ 436.9 $ 330.5 Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Unfavorable impact of foreign currency exchange rates on product sales denominated in currencies other than USD $ (107.8) $ (100.0) $ (59.0) $ (7.8) $ (41.0) The unfavorable impact of foreign currency exchange rates on USD reported results in 2024 was primarily driven by the weakening of the Argentine Peso and Japanese Yen.
The following table shows our Net Product Revenues denominated in USD and foreign currencies: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Sales denominated in USD $ 1,604.2 $ 1,366.0 $ 1,137.8 $ 238.2 $ 228.2 Sales denominated in foreign currencies 1,563.6 1,443.4 1,234.7 120.2 208.7 Total net product revenues $ 3,167.8 $ 2,809.4 $ 2,372.5 $ 358.4 $ 436.9 Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Unfavorable impact of foreign currency exchange rates on product sales denominated in currencies other than USD $ (40.7) $ (107.8) $ (100.0) $ 67.1 $ (7.8) The unfavorable impact of foreign currency exchange rates on USD reported results in 2025 was primarily driven by weakening of the Argentine Peso, Brazilian Real and Mexican Peso, partially offset by strengthening of the Euro.
See the risk factor, “Our business is affected by macroeconomic conditions.” described in “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K. Business Developments We continued to grow our commercial business and advance our product candidate pipeline during 2024.
See the risk factor, “Our business is affected by macroeconomic conditions.” described in “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K.
If the related product candidate's marketing application is rejected by the applicable regulators and the likelihood of future revenues for a product candidate become uncertain, the related manufacturing costs are expensed as R&D expenses. 64 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
If the related product candidate's marketing application is rejected by the applicable regulators and the likelihood of future revenues for a product candidate become uncertain, the related manufacturing costs are expensed as R&D expenses.
Interest Expense for the periods presented was as follows: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Interest expense $ 12.7 $ 17.3 $ 16.0 $ (4.6) $ 1.3 The decrease in Interest Expense in 2024 as compared to 2023 was primarily due to the August 1, 2024 maturity of our convertible debt (the 2024 Notes).
Interest Expense for the periods presented was as follows: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Interest expense $ 10.9 $ 12.7 $ 17.3 $ (1.8) $ (4.6) Interest Expense decreased in 2025 as compared to 2024 primarily due to settlement of 2024 Notes that matured in August 2024.
Unrecognized Tax Benefits As of December 31, 2024, our liability for unrecognized tax benefits was $325.0 million. Due to their nature, we cannot reasonably estimate the timing of future payments. See Note 1 6 to our accompanying Consolidated Financial Statements for a full discussion on our income taxes.
See Note 9 to our accompanying Consolidated Financial Statements for details on our lease liabilities. Unrecognized Tax Benefits As of December 31, 2025, our liability for unrecognized tax benefits was $380.9 million. Due to their nature, we cannot reasonably estimate the timing of future payments.
Interest Income We invest our cash equivalents and investments in U.S. government securities and other high credit quality debt securities in order to limit default and market risk.
Interest Income We invest our cash equivalents and investments in U.S. government securities and other high credit quality debt securities in order to limit default and market risk. 69 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
If such assumptions were to differ significantly, it may have a material impact on our ability to realize our net deferred tax assets. Changes in our valuation allowance will result in a change to tax expense.
If such assumptions were to differ significantly, it may have a material impact on our ability to realize our net deferred tax assets. Changes in our valuation allowance will result in a change to tax expense. 73 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Financing and Credit Facilities Our $600.0 million (undiscounted) of total convertible debt as of December 31, 2024 will impact our liquidity due to the semi-annual cash interest payments as well as the repayment of the principal amount, if not converted.
Our $600.0 million (undiscounted) of total convertible debt as of December 31, 2025 consisting of our 1.25% senior subordinated convertible notes due in 2027 (the 2027 Notes), will impact our liquidity due to semi-annual cash interest payments and repayment of the principal amount in cash at maturity in May 2027 if not converted.
Dollars, except as otherwise disclosed) In August 2024, we entered into an unsecured revolving credit facility providing for $600.0 million in revolving loan commitments. The credit facility is intended to finance ongoing working capital needs and for other general corporate purposes. The credit facility contains financial covenants including a maximum total net leverage ratio and a minimum interest coverage ratio.
Our $600.0 million unsecured revolving credit facility (Revolving Facility) as of December 31, 2025 is intended to finance ongoing working capital needs and other general corporate initiatives. The Revolving Facility matures in August 2029 and contains financial covenants including a maximum total net leverage ratio and a minimum interest coverage ratio.
The adoption of the Pillar Two framework did not have a material impact on our effective tax rate and we plan to continue evaluating additional guidance released by the OECD, along with the pending legislative adoption by additional individual countries.
Dollars, except as otherwise disclosed) on our effective tax rate and we plan to continue evaluating additional guidance released by the OECD, along with the pending legislative adoption by additional individual countries.
Dollars, except as otherwise disclosed) Financial Condition, Liquidity and Capital Resources Our cash, cash equivalents, and investments as of December 31, 2024 and 2023 were as follows: 2024 2023 2024 vs. 2023 Cash and cash equivalents $ 942.8 $ 755.1 $ 187.7 Short-term investments 194.9 318.7 (123.8) Long-term investments 521.2 611.1 (89.9) Total cash, cash equivalents and investments $ 1,658.9 $ 1,684.9 $ (26.0) We believe cash generated from sales of our commercial products, in addition to our cash, cash equivalents and short-term investments will be sufficient to satisfy our liquidity requirements for at least the next 12 months.
Financial Condition, Liquidity and Capital Resources Our cash, cash equivalents, and investments as of December 31, 2025 and 2024 were as follows: 2025 2024 2025 vs. 2024 Cash and cash equivalents $ 1,311.7 $ 942.8 $ 368.9 Short-term investments 248.9 194.9 54.0 Long-term investments 492.2 521.2 (29.0) Total cash, cash equivalents and investments $ 2,052.8 $ 1,658.9 $ 393.9 We believe cash generated from sales of our commercial products, in addition to our cash, cash equivalents and short-term investments, including proceeds from the 2034 Notes and external financings, will be sufficient to satisfy our liquidity requirements for at least the next 12 months, including our agreement to acquire Amicus in an all-cash transaction.
Although we have historically collected receivables from customers in such countries, sustained weakness or further deterioration of the local economies and currencies may cause customers in those countries to be unable to pay for our products. We will continue to monitor these conditions and will attempt to adjust our business processes, as appropriate, to mitigate macroeconomic risks to our business.
In addition, we sell our products in certain countries that face economic volatility and weakness. Although we have historically collected receivables from customers in such countries, sustained weakness or further deterioration of the local economies and currencies may cause customers in those countries to be unable to pay for our products.
R&D expense primarily includes preclinical and clinical studies, personnel and raw materials costs associated with manufacturing clinical product, quality control and assurance, other R&D activities, R&D facilities and regulatory costs.
R&D expense primarily includes preclinical and clinical studies, personnel and raw materials costs associated with manufacturing clinical product, quality control and assurance, other R&D activities, R&D facilities and regulatory costs. 67 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
The increase in net cash used in financing activities in 2024 compared to 2023 was primarily due to the $495.0 million settlement of the 2024 Notes, which matured in August 2024.
The decrease in net cash used in financing activities in 2025 compared to 2024 was primarily due to $495.0 million settlement of the 2024 Notes that matured in August 2024. The decrease was also attributable to lower proceeds from exercises of equity awards in 2025.
Management is not aware of any potential changes that would have a material effect on our Consolidated Financial Statements. See Note 1 6 to our accompanying Consolidated Financial Statements for additional discussion.
Management is not aware of any potential changes that would have a material effect on our Consolidated Financial Statements. See Note 1 5 to our accompanying Consolidated Financial Statements for additional discussion. Valuation of assets and liabilities in connection with acquisitions We have acquired and continue to acquire intangible assets in connection with business combinations and asset acquisitions.
In 2024, we achieved $2.9 billion in total revenues, including a significant contribution from our ongoing expansion of VOXZOGO, and we continued making important advancements in our product development pipeline.
Business Developments In 2025, we achieved $3.2 billion in total revenues, including a significant contribution from our ongoing expansion of VOXZOGO, and we continued to grow our commercial business and advance our product candidate pipeline.
Impairments of Long-Lived Assets We assess changes in economic, regulatory and legal conditions and make assumptions regarding estimated future cash flows in evaluating the value of our property, plant and equipment, goodwill and other long-lived assets. We periodically evaluate whether current facts or circumstances indicate that the carrying values of our long-lived assets may not be recoverable.
The fair values of identifiable intangible assets are primarily determined using the income method. Impairments of Long-Lived Assets We assess changes in economic, regulatory and legal conditions and make assumptions regarding estimated future cash flows in evaluating the value of our property, plant and equipment, goodwill and other long-lived assets.
Our San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, we pursue treatments that offer new possibilities for patients and families around the world navigating rare or difficult to treat genetic conditions.
Our San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, we seek to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients.
Gross margin increased compared to 2023 primarily due to lower per unit manufacturing costs of our enzyme products driven by improved yields. Research and Development R&D expense includes costs associated with the research and development of product candidates and post-marketing research commitments related to our commercial products.
Gross margin decreased in 2025 compared to 2024 primarily due to ROCTAVIAN inventory write-off, partially offset by increased sales volume of higher-margin products within our Enzyme Therapies portfolio. Research and Development R&D expense includes costs associated with the research and development of product candidates and post-marketing research commitments related to our commercial products.
Dollars, except as otherwise disclosed) R&D expense consisted of the following: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Research and early pipeline $ 434.0 $ 393.1 $ 313.9 $ 40.9 $ 79.2 Later-stage clinical programs 27.6 62.6 119.0 (35.0) (56.4) Marketed products 285.6 291.1 216.7 (5.5) 74.4 Total R&D expense $ 747.2 $ 746.8 $ 649.6 $ 0.4 $ 97.2 R&D expense marginally increased in 2024 compared to 2023 primarily due to higher spend in Research and early pipeline related to pre-clinical activities for new VOXZOGO indications and our prioritized pipeline.
R&D expense consisted of the following: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Research and early pipeline $ 383.7 $ 434.0 $ 393.1 $ (50.3) $ 40.9 Later-stage clinical programs 308.3 27.6 62.6 280.7 (35.0) Marketed products 229.9 285.6 291.1 (55.7) (5.5) Total R&D expense $ 921.9 $ 747.2 $ 746.8 $ 174.7 $ 0.4 R&D expense increased in 2025 compared to 2024 primarily due to higher spend on Later-stage clinical programs as a result of the $221.0 million In-Process Research and Development (IPR&D) charge following the Inozyme acquisition and continued progression of VOXZOGO for hypochondroplasia.
SG&A expenses consisted of the following: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 S&M expense $ 476.7 $ 488.4 $ 450.3 $ (11.7) $ 38.1 G&A expense 532.3 404.0 372.9 128.3 31.1 Total SG&A expense $ 1,009.0 $ 892.4 $ 823.2 $ 116.6 $ 69.2 S&M expenses by product were as follows: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Enzyme Products $ 219.0 $ 225.3 $ 225.7 $ (6.3) $ (0.4) VOXZOGO 134.1 108.9 102.3 25.2 6.6 ROCTAVIAN 76.7 104.5 73.6 (27.8) 30.9 Other 46.9 49.7 48.7 (2.8) 1.0 Total S&M expense $ 476.7 $ 488.4 $ 450.3 $ (11.7) $ 38.1 The decrease in S&M expense for 2024 compared to 2023 was primarily due to reduced activities related to ROCTAVIAN as we focused commercial efforts in the U.S., Germany and Italy to align with our updated ROCTAVIAN strategy.
Dollars, except as otherwise disclosed) SG&A expenses consisted of the following: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 S&M expense $ 530.2 $ 476.7 $ 488.4 $ 53.5 $ (11.7) G&A expense 622.8 532.3 404.0 90.5 128.3 Total SG&A expense $ 1,153.0 $ 1,009.0 $ 892.4 $ 144.0 $ 116.6 S&M expenses by product were as follows: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Enzyme Therapies $ 247.1 $ 219.0 $ 225.3 $ 28.1 $ (6.3) VOXZOGO 184.2 134.1 108.9 50.1 25.2 ROCTAVIAN 30.7 76.7 104.5 (46.0) (27.8) Other 68.2 46.9 49.7 21.3 (2.8) Total S&M expense $ 530.2 $ 476.7 $ 488.4 $ 53.5 $ (11.7) The increase in S&M expense for 2025 compared to 2024 was primarily due to increased spending related to global expansion of VOXZOGO for achondroplasia and pre-launch activities on VOXZOGO for hypochondroplasia, and higher spend on demand generating activities for Enzyme Therapies.
Our purchase obligations are primarily related to firm purchase commitments entered into in the normal course of business to procure active pharmaceutical ingredients, certain inventory-related items, certain third-party R&D services, production services and facility construction services. The amount also includes hosting fees and other enterprise resource planning (ERP) system implementation costs for which we are committed.
Our purchase obligations are primarily related to firm purchase commitments entered into in the normal course of business to procure active pharmaceutical ingredients, certain inventory-related items, certain third-party R&D services, production services and facility construction services. As of December 31, 2025, we had lease payment obligations of $57.3 million, of which $10.3 million is payable in 2026.
Our Consolidated Financial Statements have been prepared in accordance with United States (U.S.) generally accepted accounting principles (GAAP) and are presented in U.S. Dollars (USD). Overview We are a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient.
Our Consolidated Financial Statements have been prepared in accordance with United States (U.S.) generally accepted accounting principles (GAAP) and are presented in U.S. Dollars (USD). Overview We are a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions.
We expect Interest Expense to decrease over the next 12 months due to the settlement of our 2024 Notes. See Note 10 to our accompanying Consolidated Financial Statements for additional information regarding our debt. 66 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
See Note 20 to our accompanying Consolidated Financial Statements for additional information related to Inozyme acquisition. 65 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Selling, General and Administrative Sales and marketing (S&M) expense primarily consists of employee-related expenses for our sales group, brand marketing, patient support groups and pre-commercialization expenses related to our product candidates. General and administrative (G&A) expense primarily consists of corporate support and other administrative expenses, including employee-related expenses.
These increases were partially offset by lower spend on Research and early pipeline due to discontinued programs and lower spend on Marketed products mainly related to ROCTAVIAN. Selling, General and Administrative Sales and marketing (S&M) expense primarily consists of employee-related expenses for our sales group, brand marketing, patient support groups and pre-commercialization expenses related to our product candidates.
The following table summarizes our Cost of Sales and gross margin : Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Total revenues $ 2,853.9 $ 2,419.2 $ 2,096.0 $ 434.7 $ 323.2 Cost of sales $ 580.2 $ 532.1 $ 503.0 $ 48.1 $ 29.1 Gross margin 79.7 % 78.0 % 76.0 % 1.7 % 2.0 % Cost of Sales increased for 2024 compared to 2023 primarily due to higher sales volumes.
The following table summarizes our Cost of Sales and gross margin : Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Total revenues $ 3,221.3 $ 2,853.9 $ 2,419.2 $ 367.4 $ 434.7 Cost of sales $ 717.4 $ 580.2 $ 532.1 $ 137.2 $ 48.1 Gross margin 77.7 % 79.7 % 78.0 % (2.0) % 1.7 % Cost of Sales increased in 2025 compared to 2024 primarily due to $119.2 million write-off of ROCTAVIAN inventory as a result of our strategic decision in the fourth quarter of 2025 to voluntarily withdraw ROCTAVIAN from the market.
With respect to the risks posed by fluctuations of both hedged and unhedged currencies against the USD, see the risk factor “Our international operations pose currency risks, which may adversely affect our operating results and net income” in “Risk Factors” included in Part I, Item 1A of this Annual Report for additional information.
With respect to the risks posed by fluctuations of both hedged and unhedged currencies against the USD, see the risk factor “Our international operations pose currency risks, which may adversely affect our 66 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Dollars, except as otherwise disclosed) Other Expense, Net Other Expense, Net for the periods presented was as follows: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Other expense, net $ 4.7 $ 38.2 $ 13.5 $ (33.5) $ 24.7 The decrease in Other Expense, Net, in 2024 compared to 2023 was primarily due to the lower foreign currency transaction losses and decreased loss on non-marketable securities.
Other Income (Expense), Net Other Income (Expense), Net for the periods presented was as follows: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Other income (expense), net $ 9.0 $ (4.7) $ (38.2) $ 13.7 $ 33.5 The increase in Other Income (Expense), Net, in 2025 compared to 2024 was primarily due to proceeds from insurance related to damaged goods.
If actual results vary from our estimates, we will make adjustments, which would affect Net Product Revenues and earnings in the period such variances become known. 69 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Differences between the estimated variable consideration to be received and actual payments received are not expected to be material. If actual results vary from our estimates, we will make adjustments, which would affect Net Product Revenues and earnings in the period such variances become known.
Our Provision for income taxes in 2024 and 2023 consisted of state, federal and foreign current tax expense which was offset by tax benefits related to stock option exercises, foreign tax credits, and deferred tax benefits from federal orphan drug credits and federal R&D credits. See Note 1 6 to our accompanying Consolidated Financial Statements for additional information.
Provision for Income Taxes Provision for Income Taxes for the periods presented was as follows: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Provision for income taxes $ 133.6 $ 114.9 $ 20.9 $ 18.7 $ 94.0 Our Provision for Income Taxes in 2025 and 2024 consisted of state, federal and foreign current tax expense which was offset by foreign tax credits, and deferred tax benefits from federal orphan drug credits and federal R&D credits.
Results of Operations Net Product Revenues Net Product Revenues consisted of the following: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 VIMIZIM $ 739.8 $ 701.0 $ 663.8 $ 38.8 $ 37.2 VOXZOGO 735.1 469.9 169.1 265.2 300.8 NAGLAZYME 479.6 420.3 443.8 59.3 (23.5) PALYNZIQ 355.0 303.9 255.0 51.1 48.9 ALDURAZYME 183.9 131.2 128.4 52.7 2.8 BRINEURA 169.1 161.9 154.3 7.2 7.6 KUVAN 120.9 180.8 227.6 (59.9) (46.8) ROCTAVIAN 26.0 3.5 — 22.5 3.5 Total net product revenues $ 2,809.4 $ 2,372.5 $ 2,042.0 $ 436.9 $ 330.5 The increase in Net Product Revenues in 2024 as compared to 2023 was primarily attributed to the following: • VOXZOGO: higher sales volume from new patients initiating therapy across all regions; 62 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Dollars, except as otherwise disclosed) Results of Operations Net Product Revenues Net Product Revenues consisted of the following: Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 VOXZOGO $ 926.9 $ 735.1 $ 469.9 $ 191.8 $ 265.2 Enzyme Therapies: VIMIZIM 792.1 739.8 701.0 52.3 38.8 NAGLAZYME 485.4 479.6 420.3 5.8 59.3 PALYNZIQ 433.3 355.0 303.9 78.3 51.1 ALDURAZYME 208.5 183.9 131.2 24.6 52.7 BRINEURA 186.4 169.1 161.9 17.3 7.2 KUVAN 99.6 120.9 180.8 (21.3) (59.9) ROCTAVIAN 35.6 26.0 3.5 9.6 22.5 Total net product revenues $ 3,167.8 $ 2,809.4 $ 2,372.5 $ 358.4 $ 436.9 Net Product Revenues include revenues generated from our commercial products.
The increase in net cash provided by investing activities in 2024 compared to net cash used in investing activities in 2023 was primarily attributable to lower net purchases of investments, lower purchases of property, plant and equipment, and a $10.0 million milestone payment received in connection with the sale of previously sold intangible assets.
The increase in net cash used in investing activities in 2025 compared to 2024 was primarily attributable to $285.2 million net cash paid for the acquisition of Inozyme, lower net maturities of available-for-sale securities, and higher purchases of property, plant and equipment.
Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Interest income $ 74.9 $ 58.3 $ 18.0 $ 16.6 $ 40.3 The increase in Interest Income during 2024 compared to 2023 was primarily due to higher balances and higher yields on our cash equivalents and investment portfolio.
Dollars, except as otherwise disclosed) Twelve Months Ended December 31, 2025 2024 2023 2025 vs. 2024 2024 vs. 2023 Interest income $ 74.9 $ 74.9 $ 58.3 $ — $ 16.6 Interest Income during 2025 compared to 2024 was relatively flat.
We do not expect Interest Income to fluctuate significantly over the next 12 months due to anticipated interest rates and yields on our cash equivalents and investments. Interest Expense We incur interest expense primarily on our convertible debt.
We expect Interest Income to decrease over the next 12 months due to lower cash and investment balances as the pending Amicus acquisition will be financed through a combination of cash on hand and non-convertible debt financing. Interest Expense We incur interest expense primarily on our convertible debt.
We also completed a strategic portfolio assessment of research and development programs to determine which we believe have the strongest combination of scientific merit, opportunity for commercial success and potential value creation for stockholders. In September 2024, we held an Investor Day, during which we provided an overview of our new corporate strategy focused on innovation, growth, and value commitment.
We periodically conduct strategic portfolio assessment of research and development programs to determine which we believe have the strongest combination of scientific merit, opportunity for commercial success and potential value creation for stockholders. Based on such strategic portfolio assessments, certain programs that do not meet its threshold for further development and commercialization could be discontinued.
Our cash flows for each of the years ended December 31, 2024 and 2023 were as follows: 2024 2023 2024 vs. 2023 Net cash provided by operating activities $ 572.8 $ 159.3 $ 413.5 Net cash provided by (used in) investing activities $ 136.5 $ (111.2) $ 247.7 Net cash used in financing activities $ (526.4) $ (18.7) $ (507.7) The increase in net cash provided by operating activities in 2024 compared to 2023 was primarily attributed to the improved operating performance and timing of cash receipts from our customers, partially offset by the timing of payments to vendors, increased personnel-related payments resulting from our ongoing organizational redesign efforts and payments of income taxes.
Our cash flows for each of the years ended December 31, 2025 and 2024 were as follows: 2025 2024 2025 vs. 2024 Net cash provided by operating activities $ 828.0 $ 572.8 $ 255.2 Net cash provided by (used in) investing activities $ (414.2) $ 136.5 $ (550.7) Net cash used in financing activities $ (42.4) $ (526.4) $ 484.0 71 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Removed
In the first half of 2024, we focused on value creation through working to accelerate growth, optimize efficiencies and drive operational excellence, including progress in executing on key strategic priorities first outlined in January 2024.
Added
In December 2025, we entered into a definitive agreement to acquire Amicus Therapeutics, Inc. (Amicus), a publicly traded, global, biotechnology company for $14.50 per share in an all-cash transaction for a total consideration of approximately $4.8 billion.
Removed
Our new strategy includes, among other things, our plans to expand VOXZOGO for the treatment of conditions beyond achondroplasia, our initiatives to drive sustained growth of the Enzyme Therapies portfolio (ALDURAZYME, BRINEURA, NAGLAZYME, PALYNZIQ and VIMIZIM), and our decision to focus on the U.S., Germany and Italy with respect to ROCTAVIAN.
Added
The pending acquisition is expected to strengthen our commercial portfolio by adding two new therapies for the treatment of Fabry disease and late-onset Pompe disease. The transaction is expected to close in the second quarter of 2026, subject to regulatory clearances, approval by the stockholders of Amicus and other customary closing conditions.
Removed
See the risk factor, “Our success depends on our ability to manage our growth and execute our corporate strategy.” described in “Risk Factors” in Part I, Item 1A of this Annual Report.
Added
We intend to finance the transaction through a combination of cash on hand and approximately $3.7 billion of non-convertible debt financing.
Removed
Change in Presentation On January 1, 2024, we changed our presentation of foreign currency transaction gains and losses resulting from remeasurement and idle plant costs within our Consolidated Statements of Income. See Note 1 to our accompanying Consolidated Financial Statements for additional details.
Added
In December 2025, we entered into a debt financing commitment letter (the Commitment Letter) and related fee letter with certain lenders, pursuant to which the lenders have committed to provide us with debt financing up to approximately $3.7 billion (the Bridge Commitment) in the form of a 364-day senior secured bridge loan facility (Bridge Facility) for the pending acquisition of Amicus.
Removed
With respect to KUVAN, see also the risk factor “If we fail to compete successfully with respect to product sales, we may be unable to generate sufficient sales to recover our expenses related to the development of a product program or to justify continued marketing of a product and our revenues could be adversely affected.” in “Risk Factors” included in Part I, Item 1A of this Annual Report for additional information on risks we face.
Added
No amounts had been drawn or were outstanding under the Bridge Commitment as of December 31, 2025.
Removed
This increase was partially offset by lower spend in Later-stage clinical programs related to ROCTAVIAN, which was moved to Marketed products following Food and Drug Administration approval in the second quarter of 2023.
Added
In February 2026, we issued $850.0 million in aggregate principal amount of 5.5% senior unsecured notes due 2034 (the 2034 Notes), and the proceeds from the issuance were deposited into an escrow account that will be used to finance the pending acquisition of Amicus.
Removed
This decrease in S&M expense was partially offset by increased spending related to global expansion of VOXZOGO for achondroplasia.
Added
In connection with the issuance of the 2034 Notes, the Bridge Commitment was reduced from approximately $3.7 billion to $2.8 billion.
Removed
The increase in G&A expense for 2024 compared to 2023 was primarily due to severance and restructuring costs associated with our portfolio strategy review and the associated organizational redesign efforts announced in 2024, and increased bad debt expense during the fourth quarter of 2024. 65 Table of Contents Management’s Discussion and Analysis of Financial Condition and Results of Operations (continued) (In millions of U.S.
Added
In place of the Bridge Facility, we also expect to enter into a senior secured term loan facility for approximately $2.8 billion in aggregate principal and a new $600.0 million senior secured revolving credit facility in 2026 that will be executed prior to or concurrently with the closing of the pending Amicus acquisition.
Removed
Provision for Income Taxes Provision for Income Taxes for the periods presented was as follows: Twelve Months Ended December 31, 2024 2023 2022 2024 vs. 2023 2023 vs. 2022 Provision for income taxes $ 114.9 $ 20.9 $ 8.0 $ 94.0 $ 12.9 Provision for income taxes in 2024 increased compared to 2023, primarily due to taxes on higher earnings and foreign-source income taxed in the U.S.
Added
See "Financial Condition, Liquidity and Capital Resources" below for additional information. In October 2025, we announced our plan to pursue options to divest ROCTAVIAN, including exploring out-licensing opportunities. Subsequently in December 2025, we committed to a plan to voluntarily withdraw ROCTAVIAN from the market due to lower than previously anticipated commercial opportunities.
Removed
Tax expense in 2023 included additional benefits from a one-time valuation allowance release related to future royalty earnings and additional R&D credits generated.
Added
In connection with this strategic decision, we recorded approximately $240.0 million of restructuring charges in 2025 comprised of an inventory write-off, impairment of long-lived assets, severance and other costs. See Note 19 to our accompanying Consolidated Financial Statements for additional details. In July 2025, we completed the acquisition of Inozyme Pharma, Inc.
Removed
In the third quarter of 2023, we determined that it is more likely than not that the deferred tax assets related to a future royalty stream will be realized.
Added
(Inozyme), a publicly traded clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics. The acquisition is intended to strengthen our enzyme therapies portfolio by adding a late-stage enzyme replacement therapy, BMN 401 (formerly INZ-701), for the treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

11 edited+1 added−0 removed14 unchanged
Biggest changeCounterparty Credit Risks Our financial instruments, including derivatives, are subject to counterparty credit risk that we consider as part of the overall fair value measurement. Our financial risk management policy limits derivative transactions by requiring transactions to be with institutions with minimum credit ratings of A- or equivalent by Standards & Poor’s, Moody's or Fitch.
Biggest changeOur financial risk management policy limits derivative transactions by requiring transactions to be with institutions with minimum credit ratings of A- or equivalent by Standards & Poor’s, Moody's or Fitch.
However, we will not recognize such gains or losses in our Consolidated Statements of Income unless the 71 Table of Contents investments are sold or we determine that the declines in the investment’s fair values below the cost basis are a result of a credit loss, which, if any, are reported in Other Expense, Net in the current period through an allowance for credit losses.
However, we will not recognize such gains or losses in our Consolidated Statements of Income unless the 75 Table of Contents investments are sold or we determine that the declines in the investment’s fair values below the cost basis are a result of a credit loss, which, if any, are reported in Other Expense, Net in the current period through an allowance for credit losses.
As of December 31, 2024, our investment portfolio did not include any investments with significant exposure to countries that face economic volatility and weakness.
As of December 31, 2025, our investment portfolio did not include any investments with significant exposure to countries that face economic volatility and weakness.
The table below summarizes the expected maturities and average interest rates of our interest-generating investments as of December 31, 2024 (in millions of U.S.
The table below summarizes the expected maturities and average interest rates of our interest-generating investments as of December 31, 2025 (in millions of U.S.
The counterparties to these forward contracts are creditworthy multinational commercial banks, which minimizes the risk of counterparty nonperformance. We regularly review our hedging program and may, as part of this review, make changes to the program. As of December 31, 2024, we had open forward contracts with net notional amounts of $1.4 billion.
The counterparties to these forward contracts are creditworthy multinational commercial banks, which minimizes the risk of counterparty nonperformance. We regularly review our hedging program and may, as part of this review, make changes to the program. As of December 31, 2025, we had open forward contracts with net notional amounts of $1.5 billion.
Although not predictive in nature, based on our investment portfolio and interest rates for the period ending December 31, 2024, we believe a 100 basis point increase in interest rates could result in a potential loss in fair value of our investment portfolio of approximately $8.5 million. Changes in interest rates may affect the fair value of our investment portfolio.
Although not predictive in nature, based on our investment portfolio and interest rates for the period ending December 31, 2025, we believe a 100 basis point increase in interest rates could result in a potential loss in fair value of our investment portfolio of approximately $8.6 million. Changes in interest rates may affect the fair value of our investment portfolio.
A hypothetical 10% adverse movement in foreign currency exchange rates compared with the USD relative to exchange rates as of December 31, 2024 would have resulted in a reduction in the value received over the remaining life of these contracts by approximately $129.6 million on this date and, if realized, would negatively affect earnings during the remaining life of the contracts.
A hypothetical 10% adverse movement in foreign currency exchange rates compared with the USD relative to exchange rates as of December 31, 2025 would have resulted in a reduction in the value received over the remaining life of these contracts by approximately $152.9 million on this date and, if realized, would negatively affect earnings during the remaining life of the contracts.
Based on our overall foreign currency denominated exposures as of December 31, 2024, we believe that a near-term 10% fluctuation of the USD exchange rate could result in a potential change in the fair value of our net foreign currency denominated assets and liabilities, excluding our investments and open forward contracts, by approximately $32.7 million.
Based on our overall foreign currency denominated exposures as of December 31, 2025, we believe that a near-term 10% fluctuation of the USD exchange rate could result in a potential change in the fair value of our net foreign currency denominated assets and liabilities, excluding our investments and open forward contracts, by approximately $39.6 million.
During 2024, approximately 51% of our net product sales were denominated in foreign currencies and 25% of our operating expenses, excluding Cost of Sales, were denominated in foreign currencies.
During 2025, approximately 49% of our net product sales were denominated in foreign currencies and 19% of our operating expenses, excluding Cost of Sales, were denominated in foreign currencies.
Dollars): Expected Maturity 2025 2026 2027 2028 2029 Total Available-for-sale debt securities $ 194.8 $ 317.8 $ 172.4 $ 18.6 $ 7.9 $ 716.1 Average interest rate 4.6 % 4.5 % 4.6 % 4.7 % 4.6 % 4.6 % We have outstanding $600.0 million (undiscounted) of the 2027 Notes.
Dollars): Expected Maturity 2026 2027 2028 2029 2030 Total Available-for-sale debt securities $ 248.9 $ 257.2 $ 171.4 $ 47.5 $ 12.3 $ 741.2 Average interest rate 3.8 % 3.8 % 3.8 % 3.8 % 3.9 % 3.8 % We have outstanding $600.0 million (undiscounted) of the 2027 Notes.
The interest rate on the 2027 Notes is fixed and therefore does not expose us to risk related to rising interest rates. As of December 31, 2024, the fair value of our convertible debt was $558.9 million.
The interest rate on the 2027 Notes is fixed and therefore does not expose us to risk related to rising interest rates. As of December 31, 2025, the fair value of our convertible debt was $576.3 million. In February 2026, we issued $850.0 million aggregate principal amount of 5.5% senior unsecured notes due in 2034 (the 2034 Notes).
Added
The interest rate on the 2034 Notes is fixed and therefore does not expose us to risk related to rising interest rates. See Note 21 to our accompanying Consolidated Financial Statements for additional details. Counterparty Credit Risks Our financial instruments, including derivatives, are subject to counterparty credit risk that we consider as part of the overall fair value measurement.

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