Results from Ongoing CANOPY Clinical Program for VOXZOGO Showcase Impact of C-Type Natriuretic Peptide (CNP) as Master Regulator of Growth-Related Development Across Multiple Genetic Skeletal Conditions

New Data Highlight Meaningful Improvements in Health-Related Quality of Life for Children with Achondroplasia

Investigator-Led Study Shows Significant Increases in Bone Length While Maintaining Bone Strength in Children with Achondroplasia

Investigator-Led Study Observes Sustained Growth Gains in Children with Hypochondroplasia, Noonan Syndrome and Genetic Variants Associated with Idiopathic Short Stature

SAN RAFAEL, Calif., Sept. 18, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that positive data from the CANOPY clinical program evaluating VOXZOGO (vosoritide) in children with achondroplasia and other genetic skeletal conditions will be presented at the 16th International Skeletal Dysplasia Society meeting (ISDS) in Madrid, Sept. 18-21, 2024. These results include data showing that children with achondroplasia treated with VOXZOGO experienced meaningful improvements beyond height, such as in health-related quality of life (HRQoL), and increased bone length while maintaining bone strength. Researchers will also present encouraging data from ongoing investigator-led studies investigating treatment in children with other genetic skeletal conditions, including hypochondroplasia and Noonan syndrome, as well as those with genetic variants often associated with idiopathic short stature such as aggrecan (ACAN) deficiency and heterozygous NPR2 mutations.

"VOXZOGO is now becoming the standard of care in achondroplasia, based on its proven effects on growth velocity, its safety profile and the clinical data demonstrating positive impact on proportionality and quality of life in treated children with achondroplasia," said Ravi Savarirayan, M.D., Ph.D., group leader of Skeletal Biology and Disease at Murdoch Children's Research Institute in Melbourne, Australia.

Positive Impacts in Achondroplasia on Health Outcomes Including HRQoL and Maintenance of Bone Strength

Qualitative insights elucidating caregiver perspectives of children with achondroplasia revealed that VOXZOGO had positive impacts on HRQoL across several physical, emotional and social functioning domains. Notable physical functioning improvements reported included improved motor skills (e.g., higher reach, walking, running, balance and cycling) and self-care, which are particularly meaningful outcomes for children and families impacted by the condition. Psychosocial functioning outcomes included improved confidence and social interactions.

Additional results from an investigator-led analysis of BioMarin's Phase 2 111-205 study, previously shared at the 2024 International Conference on Children's Bone Health, demonstrated 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.

"VOXZOGO is the first and only approved treatment for children with achondroplasia, providing families with an option that can be initiated in infants, and we are excited to continue investigating its possibilities in other genetic skeletal conditions through our CANOPY clinical program," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "The data at ISDS continue to demonstrate the safety and efficacy of VOXZOGO, underscoring the clinical value of our approach with CNP as an effective, central regulator of growth-related development as our research seeks to transform the treatment landscape for families impacted by achondroplasia and other genetic skeletal conditions."

Investigator-Led Studies of VOXZOGO Show Promising Efficacy and Safety Data in Hypochondroplasia and Other Genetic Skeletal Conditions

Additional presentations at ISDS include efficacy data for VOXZOGO in ongoing research across genetic skeletal conditions beyond achondroplasia. Safety results were shown to be consistent with the well-characterized safety profile of VOXZOGO in achondroplasia.

Results from an investigator-sponsored study showed sustained improvement in mean annualized growth velocity (AGV) and height standard deviation (SD) in 24 children with various genetic skeletal conditions, including Noonan syndrome and those with genetic variants associated with idiopathic short stature (ACAN deficiency and heterozygous NPR2 mutations), over one year of treatment.

Updated investigator-sponsored results from the first clinical study of VOXZOGO for children with hypochondroplasia showed sustained improvement in AGV and hypochondroplasia-specific height SDs in 26 participants over one year. Treatment efficacy was similar to what had been previously seen in achondroplasia, and there were no new safety signals observed.

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

Oral Presentations

Adjuvant Therapeutic Enhances Bone Growth and Quality in Growing Mice with Moderate-to-Severe Osteogenesis Imperfecta: Exploration of a CNP Analog
Oral #C-0012
Thursday, Sept. 19, 2:05 – 2:20 p.m.

Vosoritide Increases Growth in Children with Hypochondroplasia: Phase 2 Trial Results
Oral #C-0017
Friday, Sept. 20, 2:20 – 2:35 p.m.

Vosoritide Improves Growth in RASopathies, ACAN and NPR2 Deficiency: Preliminary Data from a Phase 2 Trial
Oral #C-0022
Friday, Sept. 20, 2:35 – 2:50 p.m.

Body Composition by Bioelectrical Impedance Analysis (BIA) in Adults with Achondroplasia in CLARITY (the Achondroplasia Natural History Study)
Oral #C-0027
Saturday, Sept. 21, 9:45 – 10 a.m.

Poster Presentations

Caregiver Perspectives on Vosoritide Treatment of Children with Achondroplasia
Poster #C-0090
Thursday, Sept. 19, 3:50 – 4:50 p.m.

Examining the Effect of Vosoritide Treatment on Bone Strength in Children with Achondroplasia
Poster #C-0033
Thursday, Sept. 19, 3:50 – 4:50 p.m.

The Achondroplasia Roadmap
Poster #C-0066
Thursday, Sept. 19, 3:50 – 4:50 p.m.

Design and Objectives of the Acorn Study: A Non-Interventional Study Evaluating Long-Term Safety in Achondroplasia Children Treated with Vosoritide
Poster #C-0110
Friday, Sept. 20, 11 a.m. – 12 p.m.

About the VOXZOGO CANOPY Clinical Program

The CANOPY clinical program was designed to evaluate the potential of VOXZOGO (vosoritide) in children with various genetic skeletal conditions, including achondroplasia, hypochondroplasia, Noonan syndrome, SHOX deficiency, Turner syndrome and idiopathic short stature, with the goal of addressing the unmet needs of and expanding treatment options for children and families impacted by these conditions.

Studies underway as part of the CANOPY program beyond achondroplasia include:

• CANOPY HCH-OS, a multinational observational study in children with hypochondroplasia.
• CANOPY HCH-3, a Phase 3 randomized, placebo-controlled, double-blind multicenter study in children with hypochondroplasia.
• CANOPY ISS-OS, a multinational observational study in children with idiopathic short stature.
• CANOPY ISS-2, a Phase 2 randomized, controlled, multicenter study in children with idiopathic short stature.
• CANOPY NS, TS, SHOX-D-2, a Phase 2 study in multiple genetic skeletal conditions including Noonan syndrome, Turner syndrome and SHOX deficiency.

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.

To date, approximately 3,500 people with achondroplasia around the world have received VOXZOGO. In total, VOXZOGO is available in 44 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 . For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com.

About Achondroplasia

Achondroplasia is a rare genetic skeletal 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 , 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 .

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 at the 2024 International Skeletal Dysplasia Society meeting (ISDS), 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 (HRQoL) in children with achondroplasia, including impact on height, bone length, strength and HRQoL; the potential benefits of VOXZOGO for children with growth-related conditions beyond achondroplasia, including hypochondroplasia and Noonan syndrome, as well as those with genetic variants often associated with idiopathic short stature such as aggrecan (ACAN) deficiency and heterozygous NPR2 mutations; BioMarin's VOXZOGO CANOPY clinical program, including BioMarin's plans and expectations for clinical trials for hypochondroplasia, genetic variants associated with idiopathic short stature and other genetic skeletal conditions such as Noonan syndrome, Turner syndrome and SHOX deficiency; and BioMarin's ability to transform the treatment landscape for families impacted by achondroplasia and other genetic skeletal 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 June 30, 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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