Investigator-Sponsored Phase 2 Study Demonstrated Positive Results in Children with Noonan Syndrome, Idiopathic Short Stature and Other Growth-Related Conditions

BioMarin-Sponsored  Phase 3 Data Show Notable Mean Annualized Growth Velocity Increases in Children with Achondroplasia Who Started Treatment During Adolescence

SAN RAFAEL, Calif., May 4, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that positive new data supporting the safety and efficacy of VOXZOGO^® (vosoritide) in children with achondroplasia, as well as positive data for investigational uses in growth-related conditions, including idiopathic short stature (ISS) and Noonan syndrome, were presented at the 2024 Pediatric Endocrine Society (PES) Annual Meeting in Chicago, May 2-5, 2024. Researchers also presented results from additional studies highlighting the medicine's efficacy and impact on health-related quality of life (HRQoL) in children with achondroplasia.

New Results in ISS and Noonan Syndrome

Positive results were presented from an investigator-sponsored Phase 2 study of VOXZOGO in children 3-11 years old with several genetic growth-related conditions, including Noonan syndrome and genetic mutations associated with ISS, such as aggrecan (ACAN) deficiency, heterozygous NPR2 mutations and neurofibromatosis 1 (NF1). Results demonstrated marked improvement in annualized growth velocity (AGV) and height standard deviation (SD) across all the conditions studied. For the eight children who completed 12 months of treatment, mean AGV increased from a baseline of 3.7 cm/year to 8.5 cm/year and mean height SD changed from -3.6 SD to -2.9 SD. Of these eight children, three with NPR2 mutations had increases of 3.3, 4.8 and 9.3 cm/year; three with Noonan syndrome had increases of 3.0, 4.0 and 5.8 cm/year; and two with ACAN mutations had increases of 3.2 and 5.4 cm/year in their AGVs over baseline. Safety results were consistent with the well-characterized safety profile of VOXZOGO.

"For the first time, we are seeing evidence that VOXZOGO could positively impact growth in several different skeletal dysplasias and growth-related conditions beyond achondroplasia, including in children with Noonan syndrome and ACAN deficiency that was presented today, as well as in hypochondroplasia that was recently shared at ACMG," said Andrew Dauber, M.D., lead investigator of the study and Chief of Endocrinology at Children's National Hospital in Washington, D.C. "The safety and efficacy of VOXZOGO in achondroplasia are well-established, and we're encouraged by the new data that support its potential to have an impact for an even broader group of children."

BioMarin has several clinical trials underway for growth-related conditions. 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) by mid-year. Additionally, clinical studies in children with ISS (111-903 and 111-210) and multiple genetic short stature pathway conditions in the U.S. are anticipated to begin enrollment later this year.

Data from BioMarin's Ongoing Trials Underscore Efficacy of VOXZOGO in Achondroplasia

New Results Show Growth Increase for Children with Achondroplasia Who Initiated Treatment During Adolescence 

Data from a Phase 3 extension study of VOXZOGO in children with achondroplasia who began treatment at 10 years of age or older showed mean age- and sex-specific AGVs that were consistently higher compared to untreated children. These data examined 31 children who remained on treatment for more than three years, with a mean treatment exposure time of 3.57 years for girls and 3.87 years for boys. The mean difference in AGV between treated and untreated children across ages 10-17 was 1.47 cm/year in girls and 1.71 cm/year in boys. AGV improvement in the VOXZOGO-treated group was maintained over a longer period of time compared to an average stature population, as opposed to an expected decline in AGV after the pubertal growth spurt. Safety was consistent with previous studies of VOXZOGO in younger children, and there was no evidence of a negative effect of treatment on bone age or pubertal development. 

"While it is important to recognize the cumulative impact that can be made if treatment with VOXZOGO is initiated early, these new results are very encouraging because they show that meaningful height gains can be made even if treatment is not initiated until adolescence," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "The data presented at PES this year add to the body of evidence supporting the impact of CNP as a master regulator of bone growth and showcase VOXZOGO's potential to positively impact growth and development in a number of different growth-related conditions."

Additional Phase 2 and Phase 3 Data Demonstrate Efficacy and Suggest Positive Impact on Health-Related Quality of Life for Children with Achondroplasia

Additional data shared at PES, previously presented at the 2024 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, demonstrated the positive effects of VOXZOGO on AGV in different age groups, as well as suggested positive impact on HRQoL.

Results from a Phase 2 extension study showed that VOXZOGO maintained positive effects on linear growth over time in children who began treatment under age five. With more than seven 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. Persistent growth-promoting effects of VOXZOGO were also demonstrated in a Phase 3 extension study in children aged 5-18 with achondroplasia with up to four years of treatment follow-up.

Another Phase 3 study suggested that VOXZOGO improved HRQoL among children with achondroplasia, particularly aspects associated with physical functioning, an outcome of significant importance for children and families impacted by achondroplasia. After three 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 full list of presentations at the PES Annual Meeting include:

Investigator-Sponsored Oral Presentation

Vosoritide Improves Growth in Selected Genetic Causes of Short Stature: 12 Month Data from a Phase 2 Trial 
Oral; Abstract #: 6512
Saturday, May 4, 2024, 3 – 4 p.m. Central Time (CT)

BioMarin Poster Presentations  (all times are CT)

Growth-Promoting Effects of Vosoritide in Children with Achondroplasia ≥ 10 Years at Treatment Initiation: Results from a Phase 3 Extension Study 
Poster; Abstract #: 6813
Friday, May 3, 2024, 12:15 – 1:45 p.m.

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life
Poster; Abstract #: 6822
Friday, May 3, 2024, 12:15 – 1:45 p.m.

Persistence of Growth-Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide  
Poster; Abstract #: 6803
Friday, May 3, 2024, 12:15 – 1:45 p.m.

Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for Up to 4 years: Update from Phase 3 Extension Study  
Poster; Abstract #: 6831
Friday, May 3, 2024, 12:15 – 1:45 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 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 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 Pediatric Endocrine Society (PES) Annual Meeting, including the investigator-sponsored oral presentation and four poster presentations; the development of BioMarin's VOXZOGO program generally; the safety profile, efficacy, and potential positive impact of VOXZOGO for children with several different skeletal dysplasias and growth-related conditions beyond achondroplasia, including in children with Noonan syndrome and aggrecan (ACAN) deficiency as well as in hypochondroplasia; the potential benefits of VOXZOGO for children with achondroplasia, including the benefits to children whose treatment is initiated during adolescence, potential improvement in annualized growth velocity (AGV), and potential improvement in health-related quality of life; and the continued clinical development of VOXZOGO, including BioMarin's plans for clinical trials for 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 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 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^® and VOXZOGO^® are registered trademarks of BioMarin Pharmaceutical Inc.

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