New Data to be Presented for BioMarin's VOXZOGO® (vosoritide) in Children with Hypochondroplasia and Achondroplasia at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting

Investigator-Sponsored Phase 2 Study Demonstrated Positive Results for VOXZOGO in Children with Hypochondroplasia

New Analyses Highlight VOXZOGO 7-year Data and Improvement on Quality of Life in Children with Achondroplasia

SAN RAFAEL, Calif., March 12, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that positive early results from an investigator-sponsored Phase 2 study of VOXZOGO^® (vosoritide) in children with hypochondroplasia, will be presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Toronto, Canada, March 12-16, 2024. Researchers will also present data from Phase 2 and Phase 3 studies of the medicine in children with achondroplasia, including results that demonstrate VOXZOGO's positive impact on quality of life. 

Results in Hypochondroplasia

Andrew Dauber, M.D., will present positive results from his investigator-sponsored Phase 2 study of VOXZOGO in children with hypochondroplasia. The annualized growth velocity (AGV) increased from 5.12 cm/year during the observation period to 6.93 cm/year during the treatment period (mean difference: 1.81 cm/year, p<0.0001). No new safety signals were reported. 

"We are encouraged by preliminary results from the first study evaluating VOXZOGO in children with hypochondroplasia, suggesting the medicine has the potential to impact growth outcomes for this group of patients," said Dr. Dauber, who is the lead study author and Chief of Endocrinology at Children's National Hospital in Washington, D.C. "There are currently no approved medicines for children with hypochondroplasia, so we look forward to gathering additional data to deepen our understanding of VOXZOGO in hypochondroplasia and other growth-related conditions."

In late 2023, BioMarin launched the pivotal clinical trial program studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the company plans to enter the treatment phase (Phase 3 trial) later this year. 

New Data Highlights VOXZOGO Long-Term Efficacy, Safety and Quality of Life in Achondroplasia 

7-year Phase 2 Results in Achondroplasia

Data from two studies of VOXZOGO in children ≥5 years of age with achondroplasia demonstrated a sustained improvement in AGV for each year that the participants were treated. In the Phase 2 study with more than 7 years of follow up, the mean increase in growth across each year of age up to 16 years compared with untreated participants was 1.63 cm/year for boys and 1.33 cm/year for girls. Separate cross-sectional comparative analysis assessing increase in height over a 7-year period showed an additional height gain of 11.03 cm with use of VOXZOGO compared to matched untreated children over the same period.

4-year Phase 3 Results in Achondroplasia

The same analyses were produced for the Phase 3 trial in which children with achondroplasia have a mean treatment follow-up of 4 years. The mean increase in growth across each year of age up to 17 years was 1.73 cm/year for boys and 1.46 cm/year for girls. A separate cross-sectional comparative analysis assessing increase in height over a 3-year period showed an additional height gain of 5.75 cm with use of VOXZOGO compared to matched untreated children over the same period.

3-year Phase 3 Quality of Life Results in Achondroplasia

Results from a separate analysis of the Phase 3 study showed that VOXZOGO improved health-related quality of life (HRQoL) among children with achondroplasia, particularly those associated with physical activities. After 3 years, the mean increase in Quality of Life in Short Stature Youth (QoLISSY) physical domain score was 6.0 as reported by caregivers and 6.3 as reported by children. These improvements were even more pronounced in children who grew more (for those with ≥ 1 SD increase in height z-score, the mean increase in physical domain score was 11.4 as reported by caregivers and 8.5 as reported by children).

"The clinical results at ACMG reinforce the long-term benefit we are seeing in children treated with VOXZOGO, with a meaningful median height gain of more than 11 cm in children with achondroplasia following 7 years of treatment," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "We are particularly encouraged by new data demonstrating the potential impact height gains from VOXZOGO can have on quality of life, an outcome of incredible importance for children and families impacted by achondroplasia."

"Achondroplasia can have a negative effect on a child's quality of life, including physical, social and emotional aspects," said Melita Irving, M.D., study investigator and consultant clinical geneticist at Guy's and St. Thomas' NHS Foundation Trust in London. "Our studies showed that increasing height with long-term administration of VOXZOGO can result in meaningful improvements in quality-of-life measures for children with achondroplasia."

BioMarin's full list of presentations at ACMG includes: 

BioMarin Poster Presentations 

Persistence of Growth-Promoting Effects in Children with Achondroplasia Up to 7 Years: Update from a Phase 2 Extension Study with Vosoritide 
Poster #: P144
Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for Up to 4 Years: Update from Phase 3 Extension Study
Poster #: P139
Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life 
Poster #: P141
Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET

Persistence of Growth-Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide 
Poster #: P131
Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET

Exploring the Landscape of Phenylketonuria Education and Learning Needs of Genetics Trainees 
Poster #: P049
Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET

Reduction of Blood Phenylalanine in Participants Enrolled in OPAL, an Observational Study, Mirror Findings from the U.S.-based PRISM Population 
Poster #: P034
Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET

Investigator-Sponsored Oral Presentation 

Vosoritide Increases Growth Velocity in Hypochondroplasia: Phase 2 Trial Results 
Oral Session: O03
Thursday, March 14, 2024, 1:30 – 3 p.m. ET

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 indicated to increase linear growth in children with achondroplasia with open epiphyses. 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 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.

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 2024 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, including the six poster presentations and the investor-sponsored oral presentation; the development of BioMarin's VOXZOGO program generally; the potential benefits of VOXZOGO for children with achondroplasia, including the duration of such benefits, potential improvement in annualized growth velocity (AGV), and potential improvement in health-related quality of life; the potential efficacy of VOXZOGO for children with hypochondroplasia, including potential to impact growth outcomes; and the continued clinical development of VOXZOGO, including BioMarin's plans for launching the treatment phase of the Phase 3 trial studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. 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 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, 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.

Contacts:
Investors	Media
Traci McCarty	Andrew Villani
BioMarin Pharmaceutical Inc.	BioMarin Pharmaceutical Inc.
(415) 455-7558	(628) 269-7393

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