Vosoritide

Achondroplasia is an autosomal dominant genetic disease and the most common cause of dwarfism in humans. It results from a gain-of-function missense mutation in FGFR3 that results in a dramatic suppression of bone growth, both in volume and in length. Treatment for achondroplasia includes both surgical and pharmacological interventions, the latter of which includes C-type natriuretic peptide (CNP) analogs.

Endogenous CNP, first described in 1998, is primarily responsible for the stimulation of chondrocytes and long bone growth via activity at the NPR-B receptor, making it an attractive target in the treatment of a condition like achondroplasia. While the remarkably short half-life of endogenous CNP - 2 to 3 minutes due to its rapid degradation by endopeptidases - makes it ineffective as a therapeutic intervention, the development of a peptidase-resistant formulation has allowed for its use as a viable treatment option in achondroplasia.

Vosoritide is an analog of CNP with proline-glycine on its N-terminus to convey resistance to neutral endopeptidase. It was approved for use under the brand name Voxzogo (BioMarin Pharmaceutical Inc.) in the EU in August 2021 and the US in November 2021, becoming the first pharmacological intervention approved for the treatment of achondroplasia in both regions.

Vosoritide is indicated for the promotion of linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses.

This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).