BioMarin's VOXZOGO Hits Primary Endpoint in Phase 3 Hypochondroplasia Trial, Published in NEJM Evidence
核心洞察
BioMarin's Phase 3 CANOPY-HCH-3 trial met its primary endpoint, with VOXZOGO (vosoritide) improving annualized growth velocity by 2.33 cm/year versus placebo after 52 weeks (p<0.0001).
The study enrolled 81 children aged 3 to 17 with genetically confirmed hypochondroplasia (搜索) and also showed significant gains in standing height, height Z-score and arm span.
BioMarin has submitted a supplemental New Drug Application to the FDA seeking the first approved targeted therapy for hypochondroplasia (搜索), with a potential 2027 launch.
BioMarin Pharmaceutical has reported detailed results from the Phase 3 CANOPY-HCH-3 study showing that VOXZOGO (vosoritide) produced statistically significant improvements across multiple growth measures in children with hypochondroplasia (搜索). The data were published in NEJM Evidence and featured in a late-breaking oral presentation at the European Society for Paediatric Endocrinology (ESPE) 2026 Annual Meeting.
The global, multicenter trial enrolled 81 children ages 3 to 17 with genetically confirmed hypochondroplasia (搜索), randomly assigning them to receive daily vosoritide or placebo. The study was led by Andrew Dauber, M.D., MMSc, chief of Endocrinology and director of the Center for Precision Medicine and Genomics Research at Children's National (搜索) in Washington, D.C., and was sponsored by BioMarin.
Growth Endpoints Met at 52 Weeks
Treatment with VOXZOGO met the study's primary endpoint, producing a statistically significant improvement in annualized growth velocity (AGV) compared with placebo after 52 weeks, with a least squares (LS) mean difference of 2.33 cm/year (p<0.0001).
Secondary growth measures also favored vosoritide. Children treated with VOXZOGO showed a significant improvement in standing height (LS mean difference of 2.35 cm; p<0.0001), height Z-score (LS mean difference of 0.39 standard deviation score; p<0.0001), and arm span (LS mean difference of 1.03 cm; p=0.0082) compared with placebo. Children who received VOXZOGO also demonstrated numerical improvements in quality of life, and follow-up will continue to assess the impact of treatment over a longer term.
The overall safety profile was consistent with previous studies of VOXZOGO, with most adverse events reported as mild and no treatment-related serious adverse events identified. Participants will continue to be followed in a long-term extension study.
"These results presented in detail for the first time provide a comprehensive picture of the impact of VOXZOGO across multiple measures of growth in children with hypochondroplasia (搜索)," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "Based on this compelling body of evidence, we have submitted these data to the FDA with the goal of securing approval for the first medicine for children with hypochondroplasia."
Regulatory Submission Underway
BioMarin recently submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (搜索) for approval of VOXZOGO in hypochondroplasia (搜索), and the company said it is on track with submissions to the European Medicines Agency (搜索) and other regional health authorities. If approved, VOXZOGO would be the first targeted therapy for the treatment of hypochondroplasia, with a potential 2027 launch. The use of VOXZOGO to treat hypochondroplasia has not yet been approved by any regulatory agency.
There are currently no medicines approved by the FDA or the EMA for the treatment of hypochondroplasia (搜索). BioMarin estimates that roughly 14,000 children with hypochondroplasia within the company's global footprint may be eligible for treatment with VOXZOGO.
"Hypochondroplasia (搜索) can affect a child's growth, physical function and everyday life, with families often navigating unique challenges as they support their children's development," said Dauber, the lead study investigator. "The changes we observed in annualized growth velocity and arm span provide encouraging evidence of how children with hypochondroplasia responded to treatment throughout the study. These findings deepen our understanding of the condition while reinforcing VOXZOGO's potential as the first targeted medicine developed specifically for children with hypochondroplasia."
Mechanism and Existing Achondroplasia Indication
Hypochondroplasia (搜索) is a rare, genetic skeletal dysplasia characterized by impaired bone growth, leading to disproportionate short stature and skeletal differences that can affect the long bones, spine and other parts of the skeleton, and may impact physical functioning and overall quality of life. The condition presents with a broad and variable clinical spectrum and may include otolaryngologic and neurological complications, and is often diagnosed in toddlerhood or early school age based on clinical and radiological findings.
In children with achondroplasia (搜索), endochondral bone growth is negatively regulated due to a gain-of-function mutation in FGFR3 (搜索). 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 the only approved medicine to support the growth of children with achondroplasia (搜索) starting from birth, with international consensus guidelines recommending initiation as early as possible. First approved in 2021, VOXZOGO has helped more than 5,000 infants and children in more than 50 countries. It is approved in the U.S., Japan and Australia to increase linear growth in children of all ages with achondroplasia with open epiphyses, and 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., the achondroplasia (搜索) indication is approved under accelerated approval based on an improvement in annualized growth velocity, with continued approval potentially contingent upon verification and description of clinical benefit in confirmatory trials. An sNDA with long-term safety and efficacy data from three ongoing studies — including adult height and additional clinical outcomes beyond linear growth such as body proportionality and arm span — is under review with an FDA Prescription Drug User Fee Act (PDUFA) target action date of Feb. 28, 2027.
Dosing and Safety Considerations
VOXZOGO is administered daily as a subcutaneous injection given by a caregiver, with dosing based on body weight and adjusted by a healthcare provider following regular check-ups. The most important safety information notes that VOXZOGO may cause a temporary decrease in blood pressure in some patients; to reduce the risk of decreased blood pressure and associated symptoms such as dizziness, tiredness or nausea, patients should eat a meal and drink 8 to 10 ounces of fluid within one hour before receiving the medicine.
The most common side effects include injection site reactions (redness, itching, swelling, bruising, rash, hives and injection site pain), high levels of blood alkaline phosphatase on blood tests, vomiting, joint pain, decreased blood pressure and stomachache.
Broader Development Program
Children's National (搜索) researchers led the first-ever trial of vosoritide for short stature not caused by achondroplasia (搜索). That Phase 2 basket trial found increased growth in children with hypochondroplasia (搜索) and three other rare genetic growth disorders — RASopathies, ACAN mutations and NPR2 deficiency — while the world's first vosoritide trial for Turner syndrome (搜索) reported encouraging early growth results.
At ESPE 2026, BioMarin also presented data on vosoritide safety and effectiveness in young children with achondroplasia (搜索) aged 3 years and younger, with up to 36 months of follow-up from a Japanese post-marketing safety surveillance study.