Serum Sickness

Six abstracts accepted for presentation includes post hoc analyses and real-world evidence for ZYMFENTRA® (infliximab-dyyb) Findings reinforce clinical decision-making in long-term management of moderate-to-severe Crohn's disease and ulcerative colitis and underscore Celltrion's commitment to advancing scientific understanding in the field of IBD Findings reinforce clinical decision-making in long-term management of moderate-to-severe Crohn's disease and ulcerative colitis and underscore Celltrion's commitment to advancing scientific understanding in the field of IBD INCHEON, South Korea, April 28, 2025 -- Celltrion, Inc. today announced that six abstracts will be presented at the 2025 Digestive Disease Week® (DDW) Annual Meeting, taking place May 3-6 in San Diego, California. The oral and poster presentations will feature data including post hoc analyses of its pivotal LIBERTY studies (LIBERTY-CD and LIBERTY-UC) of ZYMFENTRA®, the first and only FDA-approved subcutaneous infliximab. "We are excited by the opportunity to present further analyses reinforcing ZYMFENTRA's clinical value for HCPs and patients," said Hetal Patel, PharmD MBA, Vice President of Medical Affairs at Celltrion USA. "With IBD management becoming increasingly individualized, we anticipate these analyses will help clarify how ZYMFENTRA performs across a wide range of patient types, from long-term drug persistence to recapture following dose escalation." The presentations reflect Celltrion's continued commitment to making comprehensive clinical and real-world evidence accessible to healthcare professionals in the U.S., supporting informed treatment decisions in a complex and evolving IBD landscape. The details of Celltrion's abstract presentations are as follows: Abstract Title Presentation Details All times PDT Endoscopic and histologic outcomes in patients with moderate-to-severe ulcerative colitis treated with subcutaneous infliximab: A post hoc analysis of the LIBERTY-UC study Poster Presentation #0035 IMIBD_POS: IBD: Controlled Clinical Trials in Humans Sunday May 4, 2025 / 12:30-13:30 Time to clinical recapture after dose escalation of subcutaneous infliximab following loss of response: A post hoc analysis of the 2-year Phase 3 LIBERTY-CD & LIBERTY-UC trials Poster Presentation #0016 IMIBD_POS: IBD: Controlled Clinical Trials in Humans Sunday May 4, 2025 / 12:30-13:30 Efficacy of subcutaneous infliximab maintenance therapy according to disease location in patients with moderate-to-severe Crohn's disease: A post hoc analysis of the Phase 3 LIBERTY-CD study Poster Presentation #0039 IMIBD_POS: IBD: Controlled Clinical Trials in Humans Sunday May 4, 2025 / 12:30-13:30 Impact of immunogenicity on 2-year clinical outcomes in patients with moderate-to-severe Crohn's disease treated with subcutaneous infliximab: A post hoc analysis of the Phase 3 LIBERTY-CD study Poster Presentation #0011 IMIBD_POS: IBD: Controlled Clinical Trials in Humans Sunday May 4, 2025 / 12:30-13:30 Characterization of patients who experience loss of response during maintenance treatment with subcutaneous infliximab: A post hoc analysis of the 2-year Phase 3 LIBERTY-CD & LIBERTY-UC trials Poster Presentation #0017 IMIBD_POS: IBD: Controlled Clinical Trials in Humans Sunday May 4, 2025 / 12:30-13:30 Nationwide population-based cohort study on the use and persistence of infliximab IV and SC in France: Riposte IBD study Poster Presentation #0014 IMIBD_POS: IBD: Comparative Effectiveness Studies Tuesday May 6, 2025 / 12:30-13:30 Notes to Editors: About ZYMFENTRA® (infliximab-dyyb) ZYMFENTRA® (infliximab-dyyb) is a prescription medicine used as an injection under the skin (subcutaneous injection) by adults for the maintenance treatment of moderately-to-severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV), Moderately-to-severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body. ZYMFENTRA was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is considered a new biologic with a first-approved subcutaneous administration form and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. Indication and Important Safety Information ZYMFENTRA® is a prescription medicine indicated in adults for maintenance treatment of: Moderately-to-severely active Crohn's disease following treatment with an infliximab product administered intravenously. Moderately-to-severely active ulcerative colitis following treatment with an infliximab product administered intravenously. Moderately-to-severely active ulcerative colitis following treatment with an infliximab product administered intravenously. It is not known if ZYMFENTRA is safe and effective in children under 18 years of age. What is the most important information I should know about ZYMFENTRA? SERIOUS INFECTIONS Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection. MALIGNANCIES Malignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants. Post-marketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types. In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. CONTRAINDICATIONS ZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension and serum sickness). HEPATITIS B VIRUS REACTIVATION TNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA and monitor patients closely. HEPATOTOXICITY Hepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued and a thorough investigation of the abnormality should be undertaken. CONGESTIVE HEART FAILURE Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF. HEMATOLOGIC REACTION Cases of leukopenia, neutropenia, thrombocytopenia and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONS In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. INJECTION SITE REACTIONS In clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. NEUROLOGIC REACTIONS Agents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop. RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTS Serious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended. RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTS Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITY Treatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop. VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS Prior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA. ADVERSE REACTIONS In clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA-treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness and leukopenia for CD. Please click for Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. About Digestive Disease Week® Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org About Celltrion, Inc. Celltrion is a leading biopharmaceutical company that specializes in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. Celltrion is a pioneer in the biosimilar space, having launched the world's first monoclonal antibody biosimilar. Our global pharmaceutical portfolio addresses a range of therapeutic areas including immunology, oncology, hematology, ophthalmology and endocrinology. Beyond biosimilar products, we are committed to advancing our pipeline with novel drugs to push the boundaries of scientific innovation and deliver quality medicines. For more information, please visit our website www.celltrion.com/en-us. and stay updated with our latest news and events on our social media: LinkedIn, Instagram, X, and Facebook. About Celltrion USA Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion's FDA-approved biosimilar products in immunology, oncology, hematology, and endocrinology include: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd), YUFLYMA®(adalimumab-aaty), AVTOZMA® (tocilizumab-anho), STEQEYMA® (ustekinumab-stba), STOBOCLO® (denosumab-bmwo), OSENVELT® (denosumab-bmwo) and OMLYCLO® (omalizumab-igec), as well as the novel biologic ZYMFENTRA® (infliximab-dyyb). Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit www.celltrionusa.com and stay updated with our latest news and events on our social media: LinkedIn. FORWARD-LOOKING STATEMENT Certain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion, Inc. and its subsidiaries that may constitute forward-looking statements under pertinent securities laws. This press release contains forward looking statements. These statements may be also identified by words such as "prepares", "hopes to", "upcoming", "plans to", "aims to", "to be launched", "is preparing", "once gained", "could", "with the aim of", "may", "once identified", "will", "working towards", "is due", "become available", "has potential to", "anticipate" the negative of these words or such other variations thereon or comparable terminology. In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion, Inc. and its subsidiaries' management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties associated with the company's business, including the risk factors disclosed in its Annual Report and/or Quarterly Reports, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such statements. Celltrion, Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws.

Company plans to submit for regulatory approval later this year SAN RAFAEL, Calif., April 2, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the Phase 3 PEGASUS trial evaluating PALYNZIQ® (pegvaliase-pqpz) met its primary efficacy endpoint, demonstrating a statistically significant lowering in blood Phe levels in adolescents aged 12-17 with phenylketonuria (PKU) compared to diet alone. Safety results were consistent with the known profile of the medicine. PALYNZIQ is the first and only enzyme therapy approved to treat adults with PKU. Detailed results from the PEGASUS study will be presented at an upcoming medical meeting and submitted to global health authorities starting later this year to request a label expansion for PALYNZIQ to include adolescents. "For more than two decades, BioMarin has made strides for people with PKU – pioneering the first treatment, bringing a meaningful new option in PALYNZIQ, and continuing to innovate as we advance our research pipeline. We are encouraged to see these positive data that build on that legacy and show how PALYNZIQ can make an impact for adolescents as they begin their transition to adult living," said Greg Friberg, M.D., executive vice president and chief research & development officer at BioMarin. "We look forward to sharing these data with the scientific community and to submitting them to global regulators with the goal of making PALYNZIQ available for younger people living with PKU." About PEGASUS PEGASUS is a Phase 3 multi-center open-label randomized controlled study evaluating the safety and efficacy of PALYNZIQ compared to diet alone in 55 adolescents aged 12-17 with phenylketonuria. The primary endpoints are change in blood Phe concentration and characterization of the safety profile in adolescents. Secondary endpoints include change in total dietary protein intake and pharmacokinetics. The study is being conducted in two parts: the primary treatment phase ranging from weeks 1-73 (Part 1), and the extension phase (Part 2), which lasts for up to an additional 80 weeks of monitoring for the PALYNZIQ arm and allows for crossover for those in the diet-only arm. For more information, please visit clinicaltrials.biomarin.com. About PALYNZIQ PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place. PALYNZIQ is approved to reduce blood Phe concentrations for adults in the U.S., for people 16 and older in the EU, Canada and Brazil, and for people 15 and older in Japan with PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management. Patient Support Accessing PALYNZIQ To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-866-906-6100 or e-mail [email protected]. For more information about PALYNZIQ, please visit . For additional information regarding this product, please contact BioMarin Medical Information at [email protected]. About Phenylketonuria PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to the lifelong strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact. PALYNZIQ U.S. Indication and Important Safety Information PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels greater than 600 micromol/L on existing management. BOXED WARNING: RISK OF ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Prescribe auto-injectable epinephrine. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at or by telephone at 1-855-758-REMS (1-855-758-7367) WARNINGS AND PRECAUTIONS Anaphylaxis Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea) Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability Other Hypersensitivity Reactions Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids ADVERSE REACTIONS The most common adverse reactions (at least 20% of patients in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients) The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients) The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients) Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients Blood Phenylalanine Monitoring and Diet Obtain blood Phe levels every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe levels during maintenance therapy Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis USE IN SPECIFIC POPULATIONS Pregnancy and Lactation PALYNZIQ may cause fetal harm when administered to a pregnant woman Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100) Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ Pediatric Use The safety and effectiveness of PALYNZIQ in pediatric patients have not been established Geriatric Use Clinical studies of PALYNZIQ did not include patients aged 65 years and older You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to FDA at 1-800-FDA-1088 or . Please see accompanying full Prescribing Information, including Boxed Warning. About BioMarin BioMarin is 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. The 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, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that offer new possibilities for people living with genetically defined conditions around the world. To learn more, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: the Phase 3 PEGASUS trial evaluating PALYNZIQ, including plans to present results at an upcoming medical conference; the safety profile and potential benefit of PALYNZIQ for adolescents, including ability to lower blood Phe levels in adolescents aged 12-17 with phenylketonuria (PKU) compared to diet alone; the development of BioMarin's PALYNZIQ program generally, including plans to submit detailed results to global health authorities later this year to request a label expansion for PALYNZIQ to include adolescents with the goal of making PALYNZIQ available to younger people living with PKU; and the continued clinical development of PALYNZIQ. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections® and PALYNZIQ® are registered trademarks of BioMarin Pharmaceutical Inc. SOURCE BioMarin Pharmaceutical Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

New data also to be presented for PALYNZIQ® (pegvaliaise-pqpz), reinforcing its value in sustaining blood Phe level reduction and improving health-related quality of life for adults with phenylketonuria SAN RAFAEL, Calif., March 20, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced positive new data from studies of VOXZOGO® (vosoritide) in children with achondroplasia and in ongoing clinical trials investigating other skeletal conditions, as well as PALYNZIQ® (pegvaliase-pqpz) in adults with phenylketonuria (PKU). The latest findings further validate the long-term benefit and established safety profiles of both medicines, which continue to play a pivotal role for people living with these genetically defined conditions. The data will be presented at the 2025 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Los Angeles. Data Highlight VOXZOGO Treatment Adherence and Favorable Safety Profile in Infants New data from a study in Japan showed strong treatment adherence with VOXZOGO in children with achondroplasia under the age of 3, with no reported treatment-related adverse events nor any dose interruptions among 63 children followed for up to 23.7 months. These real-world findings validate VOXZOGO's established safety profile and reinforce the therapeutic benefit seen in clinical studies. The study's safety results, including in infants as young as 1 month old, add to the growing body of evidence supporting early treatment initiation. "VOXZOGO is the first and only approved treatment for children with achondroplasia, and it is encouraging to see favorable safety and strong adherence in very young children receiving the medicine in real-world clinical practice. As the effects of restricted growth are apparent from birth in children with achondroplasia, we expect that earlier treatment should translate to greater benefits," said Greg Friberg, M.D., executive vice president and chief research & development officer at BioMarin. "In addition to data in achondroplasia, scientific research at ACMG furthers our genetic understanding of skeletal conditions like hypochondroplasia, in which we hope to complete enrollment for our pivotal study with VOXZOGO in the first half of 2025." PALYNZIQ Data Show Importance of Sustained Blood Phe Level Reduction and Improvement in Quality of Life in Adults with PKU New data from the OPAL study, a post-marketing observational trial to assess the real-world safety and efficacy of PALYNZIQ, showed lowered blood Phe levels following treatment and positive health-related quality of life (HRQoL) outcomes. Mean blood Phe level was 1029 μmol/L at baseline (n=51) and lowered to 293 μmol/L at week 96 (n=16), representing a 67.8% reduction. Improvements in HRQoL were also observed, as measured by the PKU quality of life questionnaire (PKU-QOL) and the PKU Symptom Severity and Impacts Scale (PKU-SSIS), which use a scale of 1-100, with lower scores indicating better HRQoL. Mean change from baseline of -12.4 and -11.8 respectively were observed over the same time period. Additionally, secondary data analyses from the Phase 3 PRISM clinical trial program demonstrated that sustaining lowered blood Phe levels with PALYNZIQ led to improvements in attention and mood. Most notably, scores for sustained Phe levels ≤120 were significantly better than those at sustained levels of ≤600 or ≤360, suggesting blood Phe in the normal range may provide additional benefit for adults living with PKU. Real-world data from the Assessment of the Treatment and management LAndScape of PKU (ATLAS) study also highlighted a shift in the treatment landscape in part attributable to PALYNZIQ, with an increased proportion of people with PKU treated across 19 U.S. clinics achieving blood Phe levels ≤360 μmol/L and a reduction in the proportion of individuals with blood Phe levels >1200 μmol/L. These findings demonstrate PALYNZIQ's efficacy in treating PKU, as the company works to advance this option for younger people living with the genetically defined condition, with results from a Phase 3 study in adolescents expected later this year. Below are BioMarin's key presentations at ACMG, all listed in Pacific Time: Interdisciplinary Variant Re-Classification: FGFR3 as an Example of Genotypic Investigation in Suspected Skeletal Dysplasia Population Poster #P213 Thursday, March 20, 10:30 – 11:30 a.m. How Helpful are Sleep Studies in Determining Surgical Need in Infants with Achondroplasia? Poster #P313 Thursday, March 20, 10:30 – 11:30 a.m. Beyond Boundaries: The Continuous Spectrum in FGFR3-Related Conditions Poster #P373 Thursday, March 20, 10:30 – 11:30 a.m. Index of Sustained Phe Response and Improvements in PKU Clinical Outcome Assessments in Patients Receiving Pegvaliase Poster #P009 Thursday, March 20, 10:30 – 11:30 a.m. Initial Psychometric Evaluation of the Adult Symptom Severity and Impacts Scale (PKU-SSIS) Using Interim Data from the OPAL Study Poster #P029 Thursday, March 20, 10:30 – 11:30 a.m. The Assessment of the Treatment and Management Landscape of Phenylketonuria Survey Study: Findings from 19 Clinics in the United States Poster #P045 Thursday, March 20, 10:30 – 11:30 a.m. Safety Profile and Adherence of Vosoritide in Young Children with Achondroplasia in Japan Poster #P208 Friday, March 21, 10:30 – 11:30 a.m. Vosoritide as a Targeted Therapy for FGFR3-Related Thanatophoric Dysplasia Poster #P354 Friday, March 21, 10:30 – 11:30 a.m. Improvements in Blood Phenylalanine and Health-Related Quality of Life Outcomes Among Adults with PKU Receiving Pegvaliase in the OPAL Study Poster #P002 Friday, March 21, 10:30 – 11:30 a.m. Occurrence of Anaphylaxis in Adult Incident Pegvaliase-Treated PKU Patients in a Post-Marketing Safety Analysis in the United States Poster #P046 Friday, March 21, 10:30 – 11:30 a.m. About Achondroplasia Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull. This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth. More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still "open," typically those under 18 years of age. Approximately 25% of people with achondroplasia fall into this category. About Phenylketonuria PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to the lifelong strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact. About VOXZOGO In children 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 FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. VOXZOGO is approved in the U.S., Japan and Australia to increase linear growth in children of all ages with achondroplasia with open epiphyses, and VOXZOGO is indicated in the EU for the treatment of achondroplasia in children 4 months of age and older whose epiphyses are not closed, as confirmed by appropriate genetic testing. In the U.S., this indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history. Patient Support Accessing VOXZOGO To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-833-VOXZOGO (1-833-869-9646) or e-mail VOXZOGOSupport@biomarin-rareconnections.com. For more information about VOXZOGO, please visit www.voxzogo.com. For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. About PALYNZIQ PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place. PALYNZIQ is approved to reduce blood Phe concentrations for adults in the U.S., for people 16 and older in the EU, Canada and Brazil, and for people 15 and older in Japan to reduce blood Phe concentrations in individuals with PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management. Patient Support Accessing PALYNZIQ To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-866-906-6100 or e-mail support@biomarin-rareconnections.com. For more information about PALYNZIQ, please visit www.palynziq.com. For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. VOXZOGO U.S. Important Safety Information What is VOXZOGO used for? VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses). VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. What is the most important safety information about VOXZOGO? VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO. What are the most common side effects of VOXZOGO? The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away. How is VOXZOGO taken? VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made. Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual. The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups. Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider. What should you tell the doctor before or during taking VOXZOGO? Tell your doctor about all of the patient's medical conditions includingIf the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. You may report side effects to BioMarin at 1-866-906-6100. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see additional safety information in the full Prescribing Information and Patient Information. PALYNZIQ U.S. Indication and Important Safety Information PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels greater than 600 micromol/L on existing management. BOXED WARNING: RISK OF ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Prescribe auto-injectable epinephrine. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367) WARNINGS AND PRECAUTIONS Anaphylaxis Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea) Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability Other Hypersensitivity Reactions Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids ADVERSE REACTIONS The most common adverse reactions (at least 20% of patients in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients) The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients) The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients) Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients Blood Phenylalanine Monitoring and Diet Obtain blood Phe levels every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe levels during maintenance therapy Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis USE IN SPECIFIC POPULATIONS Pregnancy and Lactation PALYNZIQ may cause fetal harm when administered to a pregnant woman Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100) Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ Pediatric Use The safety and effectiveness of PALYNZIQ in pediatric patients have not been established Geriatric Use Clinical studies of PALYNZIQ did not include patients aged 65 years and older You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed Warning. About BioMarin BioMarin is 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. The 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, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that offer new possibilities for people living with genetically defined conditions around the world. To learn more, please visit www.biomarin.com. Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: data to be presented at the 2025 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, including the ten poster presentations; the development of BioMarin's VOXZOGO program generally, including expectation to complete enrollment of the pivotal study with VOXZOGO in hypochondroplasia in the first half of 2025; the safety profile and potential benefits of VOXZOGO for children with achondroplasia, including the expectation that earlier treatment should lead to potentially greater benefits; the development of BioMarin's PALYNZIQ program generally; BioMarin's plans to advance PALYNZIQ for the treatment of adolescents with phenylketonuria (PKU), including expectation that results from a Phase 3 study will be available later this year; the benefits of PALYNZIQ for adults with PKU, including potential improvement in health-related quality of life; and the continued clinical development of VOXZOGO and PALYNZIQ. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of VOXZOGO and PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections®, VOXZOGO® and PALYNZIQ® are registered trademarks of BioMarin Pharmaceutical Inc. Contacts: Investors Media Traci McCarty Andrew Villani BioMarin Pharmaceutical Inc. BioMarin Pharmaceutical Inc. (415) 455-7558 (628) 269-7393 View original content to download multimedia:https://www.prnewswire.com/news-releases/biomarin-presents-new-data-demonstrating-favorable-safety-and-strong-adherence-in-real-world-clinical-practice-with-voxzogo-vosoritide-in-children-under-3-with-achondroplasia-at-2025-american-college-of-medical-genetics-and-gen-302406448.html SOURCE BioMarin Pharmaceutical Inc.