Navepegritide tied to increased growth velocity in children with ACH

Once-weekly treatment with navepegritide was associated with significantly improved annualized growth velocity (AGV) in children with achondroplasia (ACH) compared with placebo, according to results from the pivotal ApproaCH trial presented at ENDO 2025.

Navepegritide demonstrated superiority over placebo in improving AGV at week 52, said the researchers.

Navepegritide is an investigational prodrug of C-type natriuretic peptide (CNP) designed to provide a low C_max through continuous exposure of active CNP with once-weekly dosing. [EClinicalMedicine 2023;65:102258]

The researchers stated that “continuous exposure to the released CNP stimulates natriuretic peptide receptor B to counteract the constitutively active fibroblast growth factor receptor 3 characteristic of ACH.”

The ApproaCH trial included 84 children (aged 2–11 years) with ACH who were randomized in a 2:1 ratio to receive once-weekly navepegritide (100 μg/kg) or placebo for 52 weeks.

Children who received navepegritide achieved a least square (LS) mean AGV of 5.89 cm/year compared with 4.41 cm/year in those who received placebo, reflecting an LS mean difference of 1.49 cm/year (p<0.0001). [ENDO 2025, abstract OR36-05]

In terms of safety, the incidence of treatment-related adverse events (AEs) was comparable between the navepegritide and placebo arms (21.1 percent vs 25.9 percent), with nearly all reported AEs being grade 1 or 2 (approximately 99 percent). None of the AEs led to treatment discontinuation or withdrawal from the study.

Asymptomatic hypotension occurred in two participants in each treatment arm (3.5 percent with navepegritide and 7.4 percent with placebo), but these AEs were not considered treatment related.

Injection site reactions were also infrequent, occurring in 19.3 percent (0.41 events/person year) of those receiving navepegritide and 14.8 percent (0.15 events/person year) of those receiving a placebo.

This data suggests “that the design of once-weekly navepegritide as a prodrug with a low CNP C_max contributes to a favourable safety and tolerability profile, and may address the limitations of existing ACH therapies and support improved treatment adherence,” the researchers noted.

Overall, the ApproaCH trial showed that “navepegritide significantly improved linear growth in children with ACH while maintaining a safety profile comparable with placebo,” they concluded.