Vosoritide data support planned FDA submission for hypochondroplasia

BioMarin reported 3-year extension data for vosoritide (Voxzogo) in children with hypochondroplasia and early phase 1 findings for the investigational long-acting C-type natriuretic peptide (CNP) BMN 333 in achondroplasia at ENDO 2026, the Endocrine Society annual meeting in Chicago. The hypochondroplasia data come as the company prepares a supplemental New Drug Application submission to the FDA, planned for the third quarter of 2026, for a potential new indication.¹

“Importantly, we continue to observe sustained growth improvements over time and a favorable safety profile, adding to the growing body of evidence supporting VOXZOGO for this potential new indication,” Greg Friberg, MD, executive vice president and chief research and development officer at BioMarin, said in the announcement.¹

The hypochondroplasia results were from a phase 2, investigator-sponsored 3-year extension study led by Andrew Dauber, MD, and investigators at Children’s National Hospital. The study included 13 children with hypochondroplasia treated with vosoritide. According to BioMarin, mean height standard deviation score improved by 0.72 SD over 3 years. Mean annualized growth velocity increased from 4.27 cm/y at baseline to 7.24 cm/y at year 1 (P < .001) and remained above baseline through years 2 and 3.¹

The company described the safety profile as favorable, although detailed adverse event rates were not included in the announcement. Vosoritide is not approved by any regulatory agency for hypochondroplasia, and the reported data are from a small, nonregistrational extension cohort. BioMarin stated that the longer-term results will complement the recently announced topline findings from CANOPY-HCH-3, a registration-enabling phase 3 pivotal study in children with hypochondroplasia, in the planned FDA submission.¹

Hypochondroplasia is a rare skeletal dysplasia associated with impaired bone growth and disproportionate short stature. It has a variable clinical spectrum and may include neurologic and otolaryngologic complications. BioMarin stated that there are currently no FDA- or European Medicines Agency–approved medicines for hypochondroplasia.¹ For clinicians, the main unanswered questions are whether increases in growth velocity translate into durable gains in adult height, proportionality, function, and quality of life, and whether safety findings remain consistent with larger and longer treatment exposure.

Vosoritide is a CNP analog designed to promote endochondral bone growth by acting downstream of fibroblast growth factor receptor 3 (FGFR3) signaling. In achondroplasia, gain-of-function FGFR3 variants inhibit endochondral ossification and contribute to disproportionate short stature and skeletal complications.² Vosoritide is FDA approved to increase linear growth in pediatric patients with achondroplasia and open epiphyses; the US indication is under accelerated approval based on improvement in annualized growth velocity.¹,³

The regulatory basis for vosoritide in achondroplasia included a randomized, double-blind, phase 3 trial in children aged 5 to younger than 18 years with achondroplasia and open epiphyses. In that trial, once-daily subcutaneous vosoritide improved annualized growth velocity vs placebo over 52 weeks, with an adjusted mean difference of 1.57 cm/y.⁴ The prescribing information notes clinically relevant safety considerations, including transient decreases in blood pressure, injection-site reactions, vomiting, arthralgia, and abdominal pain.³

BioMarin also presented phase 1 single-ascending dose data for BMN 333 in healthy adults. BMN 333 is an investigational long-acting CNP being developed for achondroplasia. The company reported sustained systemic exposure and prolonged pharmacodynamic target engagement supportive of weekly dosing. At the maximum evaluated dose of 500 μg/kg, exposure to free CNP was more than 13-fold higher than that of another long-acting CNP agent, according to the announcement. BMN 333 was reported to be well tolerated across evaluated dose levels, with no dose-limiting toxicities or treatment-related serious adverse events.¹

Those phase 1 findings are preliminary and were generated in healthy adults rather than children with achondroplasia. BioMarin began enrolling patients in a registration-enabling phase 2/3 study of BMN 333 in April and expects an update from the dose-finding segment in 2027.¹ Until pediatric efficacy and safety data are available, the clinical relevance of weekly CNP exposure, including its effects on growth, skeletal outcomes, tolerability, and adherence, remains to be determined.

References

1. BioMarin announces new three-year VOXZOGO® (vosoritide) data in hypochondroplasia and BMN 333 early results at ENDO 2026. PR Newswire. June 16, 2026. Accessed June 16, 2026. https://www.prnewswire.com/news-releases/biomarin-announces-new-three-year-voxzogo-vosoritide-data-in-hypochondroplasia-and-bmn-333-early-results-at-endo-2026-302800847.html

2. Pauli RM. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis. 2019;14(1):1. doi:10.1186/s13023-018-0972-6

3. Voxzogo (vosoritide) prescribing information. BioMarin Pharmaceutical Inc. Accessed June 16, 2026. https://d34r3hkxgxjdtw.cloudfront.net/6f836309-d95f-42af-b717-2efa058ad82d/11d8e586-f965-4525-bc33-93c4b147f11b/11d8e586-f965-4525-bc33-93c4b147f11b_source__v.pdf

4. Savarirayan R, Tofts L, Irving M, et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet. 2020;396(10252):684-692. doi:10.1016/S0140-6736(20)31541-5