Navepegritide Boosts Growth Velocity and Shows Added Health Benefits in Achondroplasia: JAMA
A new study published in the Journal of the American Medical Association showed that navepegritide significantly increased annual growth velocity in children with achondroplasia while maintaining a safety and tolerability profile comparable to placebo. The treatment also showed additional potential health benefits beyond height growth.
Because the fibroblast growth factor receptor 3 variant is widely expressed throughout the body, achondroplasia has multisystemic effects that affect muscle, cardiorespiratory health, neurological function, and health-related quality of life. To assess benefits beyond growth that may have significant implications for complications and health-related quality of life in children with achondroplasia, this study examined the effectiveness, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide.
10 hospitals in Australia, Denmark, Canada, Ireland, Spain, New Zealand, and the US were enrolled in this trial from March to August 2023. The participants between the ages of 2 and 11 who met the eligibility requirements had their height measured at least 6 months before randomization, had achondroplasia verified by genetic testing, and were not receiving treatment with growth-promoting drugs.
Age and sex were used to stratify the enrolled subjects. All 84 individuals were examined for safety and effectiveness results, including 2 who stopped therapy; those with radiographic evidence of closed growth plates, scheduled bone surgery, severe untreated sleep apnea, or other illnesses known to impair growth were eliminated.
A 2:1 randomization was used to assign 84 kids to either navepegritide (n = 57) or a placebo (n = 27). Despite the early discontinuation of two navepegritide patients, all subjects were included in analyses. When compared to a placebo, navepegritide substantially increased annualized growth velocity at week 52 (difference 1.49 cm/year; 95% CI, 1.05–1.93; P<.001).
The tibial-femoral angle, mechanical axis deviation, fibula-tibia length ratio, and physical functioning ratings in children under 5 showed further advantages. There were no fatalities or significant side effects associated with the therapy. There were few injection site responses and no reports of fractures or clinical hypotension.
Overall, navepegritide medication produced a statistically significant increase in annualized growth velocity in children with achondroplasia in this randomized clinical study, although the safety and tolerability profile was comparable to that of a placebo.
Reference:
Savarirayan, R., McDonnell, C., Bacino, C. A., Hoernschemeyer, D. G., Legare, J. M., Abuzzahab, M. J., Hofman, P. L., Campeau, P. M., de Bergua Domingo, J. M., Ward, L. M., Smit, K., Smith, A., Mao, M., Ominsky, M. S., Freiberg, L. C., Shu, A. D., & Hove, H. B. (2025). Once-weekly navepegritide in children with achondroplasia: The APPROACH randomized clinical trial: The APPROACH randomized clinical trial. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2025.4771
