Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study

Background Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children. Methods After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03197766 ), participants were eligible to continue treatment in an open-label extension (ClinicalTrials.gov: NCT03424018 ) wherein all received 15 μg/kg vosoritide daily. Data from the CLARITY achondroplasia study provided an external untreated control population and reference data. Findings The population comprised 119 participants. Annualized growth velocity with vosoritide was similar to the average-stature population before puberty. The mean (SD) differences in annualized growth velocity across each integer age (6−16 years) between treated and untreated children were 1.84 (0.38) cm/year in boys and 1.44 (0.63) cm/year in girls. Three-year comparisons of treated versus untreated children demonstrated an additional height gain of 5.75 cm (95% confidence interval [CI]: 4.93, 6.57) with vosoritide. A significant improvement in upper-to-lower body segment ratio at 3 years of treatment was observed for participants with assessments at age <11 (females) and <12 years (males) versus population-level, age-matched, untreated controls ( p = 0.0087). The arm span-to-standing height ratio remained consistent with untreated participants. Vosoritide had a favorable safety profile with continuous treatment for up to 6 years (464.05 person years of exposure). No long-term harms or deaths were observed. Conclusions Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years. Funding This work was funded by BioMarin Pharmaceutical. • Vosoritide led to a height gain of 5.75 cm more than untreated children at 3 years • Vosoritide significantly improved upper-to-lower body segment ratio at 3 years • Vosoritide had a favorable safety profile with continuous treatment for up to 6 years Achondroplasia is a genetic skeletal disorder characterized by a short-limbed, short stature and a variety of consequent medical, functional, and psychosocial challenges over the lifespan in affected individuals. The only currently approved medication for children with achondroplasia is vosoritide, a C-type natriuretic peptide analog that has been shown to increase annual growth velocity in these children. This study looked at the long-term efficacy and safety of vosoritide in 119 children enrolled in an open-label extension study that followed the pivotal phase 3 trial. It reports sustained growth-promoting effects of vosoritide in these children with up to 6 years of treatment duration and improvement of body proportionality in younger children (aged <11–12 years). No new harms of treatment were identified. This long-term extension study of vosoritide in 119 children with achondroplasia showed durability of treatment effect over 6 years and significant improvement of body proportionality at 3 years of treatment as compared to an untreated cohort. No new harms were identified and no deaths reported.