ENDO 2026: New data adds to evidence for vosoritide in hypochondroplasia

Three-year extension data suggest sustained growth improvements with vosoritide in children with hypochondroplasia, although findings should be interpreted in the context of a small, responder-enriched extension population.

New data presented at ENDO 2026, the Endocrine Society Annual Meeting, provide further insight into the use of vosoritide (Voxzogo®; BioMarin Pharmaceutical Inc., San Rafael, CA, USA) in children with hypochondroplasia.^1,2 Vosoritide is a C-type natriuretic peptide (CNP) analog that promotes growth by inhibiting the ERK1/2-MAPK signaling pathway downstream of FGFR3.²

Hypochondroplasia is a rare genetic skeletal dysplasia associated with impaired bone growth, disproportionate short stature, and skeletal differences that may affect the long bones, spine, and other parts of the skeleton. It can also be associated with otolaryngologic and neurological complications, and there are currently no medicines approved by the FDA or European Medicines Agency for the treatment of hypochondroplasia.¹

The phase 2 study (NCT04219007) included a 6-month observation period followed by 12 months of daily subcutaneous vosoritide 15 μg/kg/day. Twenty-four children completed the core study, and those who achieved an increase in annualized growth velocity (AGV) of >1.6 cm/year compared with the observation period were eligible to enter the extension phase.

Thirteen children, including seven females and 11 with the Asn540Lys variant, entered the extension study and completed 3 years of treatment. At screening, mean age was 5.8 ± 1.1 years and mean height was −3.27 ± 0.71 standard deviation (SD). During the observation period, mean height worsened by −0.09 SD, reaching −3.36 ± 0.64 SD at Day 1 (p=0.01).

Over 3 years of vosoritide treatment, mean height improved by 0.72 SD, reaching −2.64 ± 0.79 SD at Year 3. Mean height gains were 0.44 SD in Year 1 (p<0.001), 0.09 SD in Year 2 (p=0.11), and 0.20 SD in Year 3 (p=0.01). Mean AGV increased from 4.27 ± 0.70 cm/year at Baseline to 7.24 ± 0.80 cm/year at the end of Year 1 (p<0.001). Although AGV decreased slightly in Years 2 and 3, it remained above Baseline at 5.55 ± 1.02 cm/year and 6.13 ± 1.27 cm/year, respectively.

Vosoritide was generally well tolerated, with no treatment-related serious adverse events reported. Injection site reactions were reported in 76.9% of participants during Year 1, decreasing to 23.1% during Years 2 and 3. No participants discontinued therapy during the extension phase.

The findings follow positive topline results from CANOPY-HCH-3, a registration-enabling phase 3 study of vosoritide in children with hypochondroplasia. BioMarin stated that these data are expected to support a supplemental New Drug Application submission to the FDA, planned for the third quarter of 2026.

Overall, the data presented adds to the evidence base for CNP-pathway approaches in hypochondroplasia. For clinicians, the findings are notable because they provide longer-term growth and safety data in a condition with no approved medical therapy. However, the extension phase included only children who had shown a growth response during the core study, and the investigators noted limitations including selection bias and variability in serial height measurements. Longer-term follow-up will be important to assess safety and final height outcomes.

References

1. 1. BioMarin Pharmaceutical Inc. (June 16, 2026). BioMarin announces new three-year VOXZOGO® (vosoritide) data in hypochondroplasia and BMN 333 early results at ENDO 2026 [Press release]. Available at: 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. Dauber A, et al. Vosoritide treatment in children with hypochondroplasia: Three-year results from a phase 2 extension trial. Presented at: ENDO 2026, Chicago, IL, USA, June 15, 2026. Oral Presentation #ORF47-08