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 Genomics (ACMG) Annual Clinical Genetics Meeting

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 [email protected]. For more information about VOXZOGO, please visit www.voxzogo.com. For additional information regarding this product, please contact BioMarin Medical Information at [email protected].

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 [email protected]. For more information about PALYNZIQ, please visit www.palynziq.com. For additional information regarding this product, please contact BioMarin Medical Information at [email protected].

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 including
  • 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.
• Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

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.

SOURCE BioMarin Pharmaceutical Inc.