Janet Legare, MD, Professor of Pediatrics in the Division of Genetics at the University of Wisconsin, discusses week 52 results of TransCon CNP (navepegritide) in children with achondroplasia.
Achondroplasia is a genetic disorder that prevents the changing of cartilage to bone. It is characterized by dwarfism, limited range of motion at the elbows, large head size, small fingers, and normal intelligence. Achondroplasia can cause health complications such as interruption of breathing, obesity, recurrent ear infections, and an exaggerated inward curve of the lumbar spine. More serious problems include a narrowing of the spinal canal that can pinch the upper part of the spinal cord and hydrocephalus. Some people with achondroplasia may have delayed motor development early on, but cognition is normal. Achondroplasia is caused by genetic changes in the FGFR3 gene.
Navepegritide is an investigational prodrug of C-type natriuretic peptide (CNP) designed for continuous inhibition of the overactive FGFR3 pathway. Week 52 results from the randomized, double-blind, placebo-controlled ApproaCH clinical trial of navepegritide in children with achondroplasion was recently published in JAMA Pediatrics. The trial included 84 children with achondroplasia ages 2 to 11 years, randomized to navepegritide or placebo.
Treatment with navepegritide was observed to increase annualized growth velocity (AGV) at week 52 compared to placebo. Improvements were also seen in lower-limb alignment and body proportionality, with decreased upper-to-lower body segment ratio from baseline to week 52 and improved tibial-femoral angle, mechanical axis deviation, and fibula-to-tibia length ratio from baseline to week 52 compared to placebo.
Additionally, navepegritide led to numerical improvements in Achondroplasia Child Experience Measure health-related quality of life measures compared to placebo. These benefits were achieved without accelerating bone age or negatively impacting spinal curvature.
Safety and tolerability of navepegritide were similar with placebo, with the majority of adverse events being mild or moderate. Injection site reactions were low and no symptomatic hypotension or bone fractures were observed.
Navepegritide has a Prescription Drug User Fee Act (PDUFA) Date of February 28, 2026.
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