Vosoritide

Hormonal / Clinical

Also known as: Voxzogo, BMN-111, Modified CNP, C-Type Natriuretic Peptide Analog

Natriuretic Peptide AnalogsResearch phase: FDA-approved (2021)Regulatory: FDA-approved November 2021 for achondroplasia in children ≥5 years with open growth plates (BioMarin Pharmaceuticals). EMA-approved August 2021. Once-daily SubQ injection. Available by prescription. Breakthrough therapy designation.

Mechanism

Vosoritide (brand name Voxzogo) is an FDA-approved once-daily injection for children with achondroplasia — the most common form of dwarfism. It is a modified version of C-type natriuretic peptide (CNP), a natural growth-plate signaling molecule. In achondroplasia, an overactive FGFR3 receptor suppresses bone growth. Vosoritide counteracts this by activating the NPR-B receptor, which turns on growth-promoting pathways in cartilage. In clinical trials, children grew an additional 1.5 cm/year compared to untreated children.

Technical detail

Vosoritide is a 39-amino-acid analog of C-type natriuretic peptide (CNP-39) with enhanced metabolic stability (resistant to neutral endopeptidase degradation). Mechanism: binds natriuretic peptide receptor B (NPR-B/guanylyl cyclase B) on growth plate chondrocytes, generating cGMP. cGMP activates protein kinase G (PKG), which inhibits the RAF-1/MEK/ERK MAPK cascade — the downstream effector of FGFR3 signaling. In achondroplasia, a gain-of-function mutation in FGFR3 constitutively activates MAPK, suppressing chondrocyte proliferation and hypertrophic differentiation in the growth plate. Vosoritide directly antagonizes this pathological FGFR3→MAPK signaling. Phase 3 trial (n=121): annualized growth velocity increased by 1.57 cm/year vs. placebo over 52 weeks (PMID: 33730456). Also reduces growth plate compression, restoring more normal endochondral ossification. Half-life ~30 minutes; once-daily SubQ injection maintains 24-hour growth plate signaling.

Evidence

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.
Savarirayan R, Wilcox WR, Harmatz P, Phillips J 3rd, Polgreen LE, Tofts L, et al. (2024) — Lancet Child & Adolescent Health — PMID: 37984383
In children aged 3-59 months with achondroplasia, 52 weeks of vosoritide produced a favorable safety profile dominated by mild injection-site reactions and improved change in height Z score versus placebo (least-squares mean difference 0.25; 95% CI -0.02 to 0.53).
moderate
Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.
Savarirayan R, Tofts L, Irving M, Wilcox WR, Bacino CA, Hoover-Fong J, et al. (2021) — Genetics in Medicine — PMID: 34341520
Two-year extension data showed persistent growth acceleration with vosoritide: annualized growth velocity rose from 4.26 to 5.52 cm/year in continuous-treatment participants, and no new safety signals were detected.
moderate
Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.
Savarirayan R, Tofts L, Irving M, Wilcox WR, Bacino CA, Hoover-Fong J, et al. (2020) — Lancet — PMID: 32891212
In 121 children with achondroplasia, daily vosoritide increased annualized growth velocity by 1.57 cm/year versus placebo over 52 weeks (95% CI 1.22-1.93; p<0.0001) with no treatment-related serious adverse events.
strong

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