BioMarin Presents Real-World Evidence Further Supporting Safety and Efficacy of VOXZOGO® (vosoritide) in Children with Achondroplasia at the European Society for Paediatric Endocrinology (ESPE) Meeting 2024

SAN RAFAEL, Calif., Nov. 16, 2024 /PRNewswire/ — BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced positive and consistent results from multiple real-world evidence studies of VOXZOGO^® (vosoritide) in children with achondroplasia. These results, as well as data from the investigational research program for VOXZOGO in hypochondroplasia, were presented at the 62nd Annual European Society for Paediatric Endocrinology (ESPE) Meeting in Liverpool, England, Nov. 16-18, 2024.

“The extensive clinical data supporting VOXZOGO in children with achondroplasia are well-known, and at ESPE, we shared further results in children who greatly benefited from the medicine in a real-world setting,” said Klaus Mohnike, M.D., Ph.D., pediatric endocrinologist at Children’s Hospital, Otto-von-Guericke-University in Magdeburg, Germany. “Furthermore, the breadth of clinical and real-world evidence underscores why we continue to advocate for treatment with VOXZOGO as early as possible.”

Real-world longitudinal data from the achondroplasia module of the European CrescNet registry involving 452 children at 30 centers across eight countries showed outcomes of treatment with VOXZOGO were consistent with previously reported clinical trials. The median age at time of enrollment was 6.12 years. Among 143 participants treated with VOXZOGO for 12 months, the average height increase was 6.36 centimeters (cm), with a height Z-score improvement of 0.7 compared to an achondroplasia reference population. For 73 participants treated for 24 months, the average height increase was 11.86 cm, with a height Z-score improvement of 1.15 compared to the same reference population.

In addition, in a real-world study in France that included 62 children, results from 17 children above the age of 5 (for whom data is available for 18 months after initial treatment) showed continued efficacy of VOXZOGO. The children who received VOXZOGO experienced an 8.76 cm increase in height, on average, and experienced a mean 0.56 improvement in Z-score compared to an untreated natural history population with achondroplasia and a 0.44 improvement in Z-score compared to a general U.S. population, indicating progress in height compared to the untreated population. The average annualized growth velocity was 5.85 cm/year, representing a substantial improvement in growth-related development over time. There were no discontinuations, and longer-term safety and effectiveness will continue to be monitored.

“These real-world data further reinforce the value of VOXZOGO as the first and only approved treatment for children, including infants, with achondroplasia,” said Greg Friberg, M.D., executive vice president and chief research & development officer at BioMarin. “We have now collected more than 6,000 patient-years of safety data through our industry-leading CANOPY clinical program, providing the scientific basis for the rapid development of VOXZOGO in new indications such as hypochondroplasia, where we hope to replicate our success in achondroplasia.”

Key presentations for VOXZOGO in achondroplasia and hypochondroplasia at ESPE, including two oral presentations and four poster presentations, are listed below, with all times in Greenwich Mean Time (GMT):

Oral Presentations

Phase 2 Trial of Vosoritide Use in Patients with Hypochondroplasia: Pharmacokinetic/Pharmacodynamic Analysis from 12 Month Data

Abstract #FC5.5

Saturday, Nov. 16 at 3:35 p.m.

Expansion of the CrescNet Registry Achondroplasia Module: Real-World Demographic Data and Outcomes After Up to 2 Years of Vosoritide Treatment

Abstract #FC2.6

Saturday, Nov. 16 at 3:45 p.m.

Poster Presentations

Real-World Effectiveness of Vosoritide in Children with Achondroplasia: Results from 18 Months Follow-Up in France

Abstract #P2-56

Patient-Centered Data Collection Provides Comprehensive Insights into Healthcare Resource Use in Achondroplasia: Data From the Pilot Phase of the VIrtual STudy in Achondroplasia (VISTA)

Abstract #P1-118

Design and Objectives of Study 111-902: a Multicenter, Prospective and Retrospective Observational Study of Children with Hypochondroplasia

Abstract #P3-164

Comparison of the Diagnostic Yield of Whole Exome Sequencing (WES) and Targeted Panel Sequencing for Children with Idiopathic Short Stature (ISS)

Abstract #P1-61

About the 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 3,800 infants and children with achondroplasia around the world have received VOXZOGO.

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 [email protected]. For more information about VOXZOGO, please visit www.voxzogo.com. For additional information regarding this product, please contact BioMarin Medical Information at [email protected].

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 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

BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. The San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin pursues treatments that offer new possibilities for patients and families around the world navigating rare or difficult-to-treat genetic conditions. To learn more, 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 presented at European Society for Paediatric Endocrinology (ESPE) 2024, including the oral and poster presentations; VOXZOGO’s efficacy, safety and impact on children with achondroplasia, including the potential benefits of early treatment with VOXZOGO; the potential benefits of VOXZOGO for children with hypochondroplasia; the development of BioMarin’s VOXZOGO program generally, including BioMarin’s ability to rapidly develop of VOXZOGO in new indications such as hypochondroplasia; and BioMarin’s CANOPY clinical program, including BioMarin’s plans and expectations for clinical trials for various genetic skeletal conditions, including achondroplasia, hypochondroplasia, Noonan syndrome, SHOX deficiency, Turner syndrome and idiopathic short stature. 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 September 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.

Contacts:

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