BioMarin to Present Data Showing Long-Term Benefit of VOXZOGO® (vosoritide) on Growth in Children with Achondroplasia at 2023 European Society for Paediatric Endocrinology (ESPE) Meeting

Label Expansion Decisions Expected from U.S. and European Regulatory Authorities in Q4

SAN RAFAEL, Calif., Sept. 21, 2023 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN), a global biotechnology company dedicated to transforming lives through genetic discovery, today announced that new data on VOXZOGO^® (vosoritide) in children with achondroplasia will be presented at the 61st Annual European Society for Paediatric Endocrinology (ESPE) Meeting in The Hague, Netherlands.

In an open-label, long-term Phase 2 extension study, VOXZOGO demonstrated consistent and durable growth benefits in young children with achondroplasia when initiated before the age of 5. Over a four-year period, children aged 2 years and above who received VOXZOGO exhibited a mean (average) height Z-score improvement exceeding 1 standard deviation compared to control groups and a height gain of more than 6 centimeters (cm) during this time period. Additionally, children under the age of 2 years, treated with VOXZOGO for three years, demonstrated substantial height gains, reflected in a mean height Z-score improvement of 0.79 standard deviations compared to controls and a height gain of more than 3 cm during this time period. Both groups of treated children demonstrated substantial restoration of height when compared to untreated children with achondroplasia.

VOXZOGO is currently approved in Europe in children with achondroplasia who are 2 years of age and older with open growth plates. Last week, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending marketing authorization to expand the indication for VOXZOGO for injection to treat children with achondroplasia aged 4 months and older whose epiphyses (growth plates) are not closed. VOXZOGO is also currently approved in the United States in children with achondroplasia who are 5 years of age and older with open growth plates. The U.S. Food and Drug Administration (FDA) has set a PDUFA Target Action Date of Oct. 21, 2023, for the company's Supplemental New Drug Application (sNDA) for VOXZOGO to expand treatment in the U.S. to include children with achondroplasia under 5 years of age.

"The data presented add to the growing body of evidence demonstrating the positive effect on growth in younger children with achondroplasia who receive VOXZOGO," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "The results showed that, over the course of four years, young children treated earlier with VOXZOGO exhibited substantial gains in height, suggesting that VOXZOGO had a significant and positive impact on their growth."

New data also highlighted real-world safety and effectiveness of VOXZOGO. Results from an early access program in France found that VOXZOGO treated under real-world conditions had a safety and effectiveness profile consistent with clinical trials. After 12 months of treatment with VOXZOGO, boys demonstrated a mean (average) increase in height with a Z-score improvement of 0.3 standard deviations, and girls showed a mean increase in height with a Z-score improvement of 0.4 standard deviations.

Key VOXZOGO presentations at ESPE include:

Oral Presentations:

Real-world Safety and Effectiveness of Vosoritide: Results from an Early Access Program in France 
RFC4.5
Thursday, September 21, 2023, 2:45 – 2:50 p.m., Central European Summer Time

Persistence of Growth Promoting Effects in Infants and Toddlers with Achondroplasia: Results in Children Aged Over 2 Years Old from a Phase II Extension Study with Vosoritide
FC4.6
Thursday, September 21, 2023, 3:45 – 3:55 p.m., Central European Summer Time

Poster:

Design and Objectives of the Acorn Study: A Non-Interventional Study Evaluating Long-Term Safety in Achondroplasia Patients Treated with Vosoritide      
T8
Thursday, September 21, 2023, 12:55 – 2:25 p.m., Central European Summer Time

About VOXZOGO (vosoritide) for Injection

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 fibroblast growth factor receptor 3 gene (FGFR3). VOXZOGO, a C-type natriuretic peptide (CNP) analog, represents a new class of therapy, which acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.

Through BioMarin's broad clinical development program, the company has enrolled 250 children with achondroplasia from eight countries in seven clinical studies evaluating the safety and efficacy of VOXZOGO.

VOXZOGO is approved in the U.S. and indicated to increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses. This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication 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.

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 fibroblast growth factor receptor 3 gene (FGFR3), 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.

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 who are 5 years of age and older with open growth plates (epiphyses).
• It is not known if VOXZOGO is safe and effective in children with achondroplasia under 5 years of age.
• 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), 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.

About BioMarin

Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, 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: the data BioMarin plans to present at ESPE, including the two oral and one poster presentations; the development of BioMarin's VOXZOGO program, including BioMarin's expectations regarding FDA's PDUFA Target Action Date with respect to its sNDA for VOXZOGO to expand treatment in the United States to include children with achondroplasia under 5 years of age; the potential impact and benefits of VOXZOGO for children with achondroplasia; and the continued clinical development of VOXZOGO. 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; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the FDA, the EMA, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, 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® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc.

SOURCE BioMarin Pharmaceutical Inc.