BioMarin to Present Data Highlighting Significant Impact of VOXZOGO® (vosoritide) in Bone Health and Health-Related Quality of Life in Achondroplasia at 2024 International Conference on Children's Bone Health

New Investigator-Led Study Shows VOXZOGO Significantly Increased Bone Length While Maintaining Bone Strength Through 5 Years of Observation in Children with Achondroplasia

Phase 2 and 3 Data on VOXZOGO Demonstrate Safety, Efficacy and Impact on Proportionality and Health-Related Quality of Life for Children with Achondroplasia

New Research Underscores Unmet Medical Needs of People with Hypochondroplasia

SAN RAFAEL, Calif., June 17, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced the presentation of new data from an investigator-led analysis of the Phase 2 111-205 study, which demonstrate that children with achondroplasia treated with VOXZOGO® experienced increases in bone length while maintaining bone strength. The data will be presented at the 11th International Conference on Children's Bone Health (ICCBH) in Salzburg, Austria, June 22-25, 2024. BioMarin will also share the first results from a study underscoring the unmet medical needs of people living with hypochondroplasia.

"With thousands of children treated since approval, the breadth and depth of data collected from our trials demonstrate VOXZOGO's safety and benefit in children of all ages, including those under 5 who have received VOXZOGO for up to four years," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "CNP is emerging as a natural and holistic regulator of statural development, and safety and efficacy data presented to date illustrate VOXZOGO's positive impact on bone growth, proportionality and quality of life. Based on this extensive evidence, we are accelerating the development of VOXZOGO across a multitude of growth-related conditions with significant unmet need."

Significant Impact on Bone Length, Strength, Proportionality and Health-Related Quality of Life in Achondroplasia

Results from an investigator-led analysis of BioMarin's Phase 2 111-205 study found that children who received VOXZOGO (n=30) had significant increases in bone length and metacarpal cortical area after approximately five years of therapy, suggesting that treatment allowed the bone to remain strong as it lengthened.

"In order for children with achondroplasia to experience meaningful changes in daily functioning following treatment to enable growth, it is critical that bone robustness is maintained to preserve strength," said Cathleen Raggio, M.D., a pediatric orthopedic surgeon at the Hospital for Special Surgery in New York. "With this study, for the first time we have shown that treatment with VOXZOGO enabled bones to remain strong as they lengthened, which is promising as we continue to better understand the impact of this therapeutic advancement."

Additional data to be presented at ICCBH, previously shared at the 2024 Pediatric Endocrine Society Annual Meeting, showcase VOXZOGO's efficacy, safety and impact on health-related quality of life in children with achondroplasia. Data observed in the Phase 3 111-301 and 111-302 studies suggest that VOXZOGO can have the potential to improve health-related quality of life among children with achondroplasia, particularly in aspects associated with physical functioning, an outcome of significant importance for children and families impacted by achondroplasia. Phase 2 and Phase 3 data also demonstrated consistent positive effects on linear growth and improvement in proportionality in children of all ages with growth potential, with follow-up conducted up to four years after the initiation of VOXZOGO treatment. Safety results were consistent with the well-characterized safety profile of VOXZOGO.

Data Underscore Unmet Needs in Hypochondroplasia

Data from a retrospective, real-world matched cohort study using electronic medical records from England showed that comorbidity event rates (e.g., respiratory, cardiovascular, orthopedic and mental health-related events) were higher in people living with hypochondroplasia (n=610) compared to people living without the condition (n=2440). General practitioner visits (median annual visits = 11.2 vs. 5.4, risk ratio [RR] = 1.8), hospital in-patient admissions (RR=5.5) and average length of hospital stay (5.6 vs. 3.8 days) were all greater as well. Most people evaluated in the study were aged 16-65 at the start of follow up. These data suggest there is a significant burden of disease amongst people of all ages with hypochondroplasia, highlighting the need for proactive management and linkage to care.

VOXZOGO Clinical Development Program Milestones

Building on its leadership in achondroplasia, BioMarin has several clinical trials underway for hypochondroplasia, idiopathic short stature (ISS) and other growth-related conditions.

A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the first patient is on track to be dosed in the treatment phase (Phase 3 trial) in June with enrollment completion expected in early 2025.

The company's observational study in children with ISS (111-903) has begun enrolling patients, and the Phase 2 treatment arm will also begin enrollment later this year (111-210). Additionally, a study in multiple other genetic short stature conditions, including Turner syndrome, SHOX deficiency, and Noonan syndrome, is anticipated to begin enrollment later this year.

Key presentations at ICCBH are listed below, with all times in Central European Summer Time (CEST):

Oral Presentations

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life
Oral #OC4.3
Monday, June 24, 2024, 3:45 – 4:45 p.m.

A Promising Adjuvant Treatment for Growing Mice with Moderate-to-Severe Osteogenesis Imperfecta: A Pilot Study of a CNP Analog
Oral #OC5.3
Tuesday, June 25, 2024, 1:30 – 2 p.m.

Poster Presentations

Does Vosoritide Treatment Affect Bone Strength in Children with Achondroplasia?
Poster #P151
Sunday, June 23, 2024, 12 – 1 p.m.

Persistence of Growth Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide
Poster #P79
Sunday, June 23, 2024, 12 – 1 p.m.

Design and Objectives of the Acorn Study: A Non-Interventional Study Evaluating Long-Term Safety in Achondroplasia Children Treated with Vosoritide
Poster #P91
Sunday, June 23, 2024, 12 – 1 p.m.

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for up to 4 Years: Update from Phase 3 Extension Study
Poster #P78
Monday, June 24, 2024, 12 – 1 p.m.

Comorbidity and Mortality Burden Among Patients with Hypochondroplasia in England between 1998-2019
Poster #P176
Monday, June 24, 2024, 12 – 1 p.m.

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. and Japan 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.

To date, more than 3,000 people with achondroplasia around the world have received VOXZOGO. In total, VOXZOGO is available in 43 markets worldwide.

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 Achondroplasia

Achondroplasia is a rare genetic growth-related condition caused by a variation in the FGFR3 gene. It is characterized by disproportionate short stature and a potentially high burden of complications related to impaired endochondral bone growth.

Approximately 80% of children with achondroplasia are born to parents of average stature as a result of a spontaneous variation in the FGFR3 gene. The worldwide incidence of achondroplasia is around one in 25,000 live births.

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.

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 the 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: data to be presented at the 11th International Conference on Children's Bone Health (ICCBH), including the oral and poster presentations; the development of BioMarin's VOXZOGO program generally; VOXZOGO's efficacy, safety and impact on health-related quality of life in children with achondroplasia, including impact on bone length, strength and health-related quality of life; the potential benefits of VOXZOGO for children with growth-related conditions beyond achondroplasia, including hypochondroplasia and idiopathic short stature; potential unmet needs in hypochondroplasia; and the continued clinical development of VOXZOGO, including BioMarin's plans for clinical trials for hypochondroplasia, idiopathic short stature and other growth-related conditions. 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 pre-clinical 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 Food and Drug Administration, 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 Quarterly Report on Form 10-Q for the quarter ended March 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 VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc.

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