ESPEYB19 5. Bone, Growth Plate and Mineral Metabolism Novel treatments for rare skeletal disorders (3 abstracts)
5.3. 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 , Font RU , Harmatz P , Rutsch F , Bober MB , Polgreen LE , Ginebreda I , Mohnike K , Charrow J , Hoernschemeyer D , Ozono K , Alanay Y , Arundel P , Kotani Y , Yasui N , White KK , Saal HM , Leiva-Gea A , Luna-González F , Mochizuki H , Basel D , Porco DM , Jayaram K , Fisheleva E , Huntsman-Labed A & Day JRS
Genet Med. 2021 Dec;23(12):2443-2447.Abstract: https://pubmed-ncbi-nlm-nih-gov.proxy.kib.ki.se/34341520/
In brief: In achondroplasia, longitudinal bone growth is inhibited resulting in severe, disproportionate short stature. In this open-label extension study of participants from the phase 3 study, daily subcutaneous injection of vosoritide during 104 weeks resulted in increase in growth velocity and a small but significant improvement in body proportions.
Commentary: Achondroplasia is caused by autosomal activating mutation in the fibroblast growth factor receptor 3 gene (FGFR3) resulting in constitutively activation of the mitogen-activated protein kinase (MAPK)–extracellular signal-regulated kinase pathway in chondrocytes and therefore inhibited endochondral ossification. C-type natriuretic peptide, encoded by NPPC, and its receptor, natriuretic peptide receptor 2 (NPR2), are potent stimulators of endochondral ossification at the level of the growth plate. Vosoritide is a recombinant C-type natriuretic peptide analogue with extended half-life that improve growth in children with achondroplasia and was recently approved for the treatment of achondroplasia in growing children aged 2 years and older.
In this extention study following the placebo-controlled phase 3 study, all 119 children (n = 58 from the active arm and n = 61 from the placebo arm) received subcutaneous vosoritide at a dose of 15.0 μg/kg/day. The study present data at the one year follow-up of the extension study, which corresponds to two years on treatment for children originally randomized to vosoritide and one year on treatment for children who crossed over to vosoritide from placebo. The improvement of growth velocity observed in children treated with vosoritide in the phase 3 study was maintained with an annualized growth velocity of 5.75±1.84 cm/year at week 78 and 5.52±1.77 cm/year at week 104. Children who crossed over from placebo to vosoritide similarily increased their growth velocity to 5.97±1.83 cm/year at week 78 and 5.43±2.03 cm/year at week 104. In addition, a small but significant improvement in body proportions (upper-to-lower body segment ratio) is reported.
The improvement in body proportion is minimal and seems hardly clinically significant. However, from the presented data, it appears that it may be continous and could therefore potentially lead to clinically meaningful improvements of body disproportion with extended duration of treatment. With time, this and other studies will reveal if vosoritide provide other beneficial effects for individuals with achondroplasia.
Volume 19
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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