Navepegritide becomes the first and only once-weekly treatment to increase linear growth in children with achondroplasia.
The FDA has approved navepegritide (Yuviwel; Ascendis Pharma) for children aged 2 years and older with achondroplasia and open growth plates under the agency's Accelerated Approval Program, according to a news release from Ascendis Pharma. The once-weekly subcutaneous injection represents the first achondroplasia therapy designed to provide continuous systemic exposure to C-type natriuretic peptide (CNP) over the entire weekly dosing interval.1
"The approval of once-weekly [navepegritide] is a major step forward in the treatment of children with achondroplasia, giving physicians for the first time the option of prescribing a once-weekly medicine backed by compelling efficacy and excellent tolerability data from 3 randomized, double-blind, placebo-controlled clinical trials," Carlos Bacino, MD, FACMG, professor of molecular and human genetics at Baylor College of Medicine and Texas Children's Hospital, noted in the news release.1
The approval was based on results from the ApproaCH randomized, double-blind, placebo-controlled phase 2b trial (NCT05598320), which enrolled 84 children aged 2 to 11 years with genetically confirmed achondroplasia. Participants were randomly assigned to receive navepegritide 100 micrograms per kilogram once weekly or placebo for 52 weeks.2,3
The trial met its primary endpoint, demonstrating superiority of navepegritide in annualized growth velocity at week 52 versus placebo. Children treated with navepegritide achieved a least-squares (LS) mean annualized growth velocity of 5.89 centimeters per year (cm/year) compared with 4.41 cm/year for placebo, a difference of 1.49 cm per year (95% CI, 1.05–1.93; P < .001).2
Treatment effects were observed across age subgroups. In children younger than 5 years (n = 31), the LS mean difference between navepegritide and placebo was 1.02 cm/year (95% CI, 0.29–1.74). In children aged 5 years and older (n = 53), the difference was 1.78 cm per year (95% CI, 1.22–2.33).2
Benefits extending beyond linear growth were observed, including improvements in skeletal alignment and health-related quality of life. Lower limb malalignment improved with navepegritide compared with placebo, as evidenced by reductions in tibial-femoral angle (LS mean difference, −1.81°; 95% CI, −3.16 to −0.47) and mechanical axis deviation (LS mean difference, −2.78 millimeters; 95% CI, −4.71 to −0.86).2
Common adverse events (AEs) in the navepegritide group included pyrexia (35.1%), nasopharyngitis (31.6%), otitis media (24.6%), upper respiratory tract infection (19.3%), vomiting (19.3%), and headache (17.5%). Injection site reactions occurred in 19.3% of navepegritide-treated participants compared with 14.8% receiving placebo. All injection site reactions were transient and mild, with none leading to treatment changes.2
Trial Name: A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With Achondroplasia (ApproaCH)
ClinicalTrials.gov ID: NCT05598320
Sponsor: Ascendis Pharma Growth Disorders A/S
Completion Date: August 13, 2025
Achondroplasia is the most common skeletal dysplasia, affecting approximately 1 in 20,000 to 30,000 live births worldwide and accounting for nearly 90% of disproportionate short stature cases. The condition results from activating mutations in the fibroblast growth factor receptor 3 gene (FGFR3), which impairs endochondral ossification of long bones.4,5
While historically considered primarily a bone growth disorder, achondroplasia is increasingly recognized as a multisystemic condition. The FGFR3 variant is expressed throughout the body, leading to complications affecting muscle, neurological function, and cardiorespiratory health. Medical complications can include foramen magnum stenosis, spinal stenosis, sleep-disordered breathing, chronic ear infections, hip problems, leg bowing, and chronic pain.4,5
Navepegritide is a prodrug of CNP administered once weekly via subcutaneous injection. The therapy leverages TransCon technology, which transiently links an inert carrier to CNP. Following administration, autocleavage of the linker occurs under physiologic pH and temperature, providing sustained release and continuous systemic exposure to active CNP throughout the week.2
Pharmacists will play important roles in supporting families initiating navepegritide therapy. Considerations include patient and caregiver education on proper storage, preparation, and subcutaneous injection technique, and counseling on the importance of weekly dosing adherence to maintain continuous CNP exposure. Furthermore, pharmacists can employ monitoring for injection site reactions and other AEs, coordinate with prescribers regarding dose adjustments as children grow, and provide information from the Ascendis Signature Access Program patient support services.1
The once-weekly dosing schedule represents a significant advantage over daily injection regimens. Vosoritide (Voxzogo; BioMarin Pharmaceutical), the only other FDA-approved pharmacologic treatment for achondroplasia, requires daily subcutaneous injections. The reduced injection frequency may improve treatment adherence and decrease injection-related complications.4
Continued approval for navepegritide is contingent upon verification and description of clinical benefit in confirmatory trials. An ongoing open-label extension study is evaluating long-term safety and efficacy. Ascendis expects commercial availability during the early part of the second quarter of 2026.1,2
