Savarirayan, RaviTofts, LouiseIrving, MelitaWilcox, William R.Bacino, Carlos A.Hoover-Fong, JulieFont, Rosendo UllotHarmatz, PaulRutsch, FrankBober, Michael B.Polgreen, Lynda E.Ginebreda, IgnacioMohnike, KlausCharrow, JoelHoernschemeyer, DanielOzono, KeiichiAlanay, YaseminArundel, PaulKotani, YumikoYasui, NatsuoWhite, Klane K.Saal, Howard M.Leiva-Gea, AntonioLuna-Gonzalez, FelipeMochizuki, HiroshiBasel, DonaldPorco, Dania M.Jayaram, KalaFisheleva, ElenaHuntsman-Labed, AliceDay, Jonathan R. S.2023-02-212023-02-212021-01-0110.1038/s41436-021-01287-7https://hdl.handle.net/11443/2830http://dx.doi.org/10.1038/s41436-021-01287-7Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 mu g/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.ArticleWOS:000680348600002