Vosoritide improves growth velocity in children with hypochondroplasia, phase 3 trial shows

A phase 3 trial of vosoritide, the C-type natriuretic peptide analog marketed as Voxzogo for achondroplasia, has met its primary endpoint in children with hypochondroplasia, another FGFR3-related dysplasia with no targeted therapy.¹ Results from the CANOPY-HCH-3 study were published in NEJM Evidence and presented at the European Society for Paediatric Endocrinology 2026 Annual Meeting.¹,²

“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,” said Andrew Dauber, MD, lead study investigator and chief of endocrinology at Children's National in Washington, DC.²

Trial design and efficacy in the vosoritide phase 3 hypochondroplasia study

CANOPY-HCH-3 was a randomized, double-blind, placebo-controlled trial at 23 sites across 9 countries.¹ Eighty-one children 3 to younger than 18 years with confirmed hypochondroplasia and a height at least 2 SD below average for age and sex were assigned 1:1 to once-daily subcutaneous vosoritide (n=41) or placebo (n=40) for 52 weeks, dosed by weight band.¹

At week 52, the least squares mean change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus −0.39 cm/year with placebo, a between-group difference of 2.33 cm/year (95% CI, 1.85-2.82; P<.0001), meeting the primary endpoint.¹,² Vosoritide also produced statistically significant gains in standing height (2.35 cm more than placebo), height Z-score (0.39 more than placebo), and arm span (1.03 cm more than placebo; all P<.05).¹,² Upper-to-lower body segment ratio and caregiver-reported quality-of-life scores did not reach significance under the trial's hierarchical testing procedure, though point estimates favored vosoritide.¹

Disease burden of hypochondroplasia in children

Hypochondroplasia is a rare, autosomal dominant dysplasia caused by gain-of-function FGFR3 variants that impair endochondral bone growth, producing disproportionate short stature, relative macrocephaly, and, in some children, developmental delay or seizures.¹ Prevalence estimates range from 0.2 per 100,000 to 1 in 15,000, though the true figure is likely underestimated because of frequent misdiagnosis.¹ BioMarin estimates roughly 14,000 children within its global footprint may be eligible for treatment if approved.² Management to date has been limited to growth hormone (approved only in Japan), supportive care, and limb-lengthening surgery.¹

Mechanism of action and prior approvals for vosoritide

Vosoritide binds the C-type natriuretic peptide receptor to inhibit the mitogen-activated protein kinase pathway downstream of FGFR3 activation in chondrocytes, counteracting the signaling defect shared by achondroplasia and hypochondroplasia.¹ It has been approved for achondroplasia in the US, EU, Japan, Brazil, Australia, and Canada since 2021, treating more than 5000 children.¹,³ A phase 2 trial in prepubertal children with hypochondroplasia previously showed similar gains without treatment-related serious adverse events; phase 3 confirms this at scale.⁴

Interpreting the phase 3 hypochondroplasia growth data

Safety in CANOPY-HCH-3 was consistent with vosoritide's profile in achondroplasia: most adverse events were mild, with no grade 3 or higher events, discontinuations, or deaths in either arm.¹ Injection-site and hypersensitivity reactions occurred somewhat more often with vosoritide but were transient; the trial's single serious adverse event, a hypochondroplasia-related seizure, occurred in the placebo group.¹ Serum collagen X marker, a biomarker of endochondral bone formation, rose substantially with vosoritide and remained elevated at week 52, consistent with a durable, on-target effect.¹

Limitations and next steps for vosoritide in hypochondroplasia

The 52-week duration does not permit conclusions about final adult height, and the trial excluded children younger than 3 years and those with milder short stature (Z-score better than −2.0), potentially missing an earlier window for intervention.¹ Body proportion and quality-of-life measures, which took 3 years to show benefit in achondroplasia trials, were not powered to detect change over 1 year.¹ Participants are continuing in an open-label extension study, and a separate phase 2 trial is evaluating vosoritide in children younger than 3 years.¹ BioMarin has submitted a supplemental new drug application to the FDA for this indication, with EMA submissions underway; if approved, vosoritide would be the first targeted therapy for hypochondroplasia, with a potential 2027 launch.²

References

1. Dauber A, Savarirayan R, Campeau PM, et al. A phase 3 trial of vosoritide in children with hypochondroplasia. NEJM Evid. Published online September 9, 2026. doi:10.1056/EVIDoa2600257

2. BioMarin Pharmaceutical Inc. BioMarin announces positive results of phase 3 VOXZOGO (vosoritide) study in hypochondroplasia published in NEJM Evidence. News release. September 9, 2026. Accessed September 9, 2026. investors.biomarin.com

3. US Food and Drug Administration. FDA approves first drug to improve growth in children with most common form of dwarfism. November 19, 2021. Accessed September 9, 2026. fda.gov

4. Dauber A, Zhang A, Kanakatti Shankar R, et al. Vosoritide treatment for children with hypochondroplasia: a phase 2 trial. EClinicalMedicine. 2024;71:102591. doi:10.1016/j.eclinm.2024.102591