FDA Approves Once-Weekly YUVIWEL for Achondroplasia in Children

The U.S. Food & Drug Administration has granted approval under the FDA's Accelerated Approval Program for YUVIWEL (navepegritide; developed as TransCon CNP), the first and only once-weekly treatment indicated to increase linear growth in children 2 years of age and older with achondroplasia with open epiphyses and the only one to provide continuous systemic exposure to CNP over the weekly dosing interval. Continued approval for this indication, which was based on an improvement in annualized growth velocity (AGV), may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Commercial availability is expected during the early part of Q2 2026. With this approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher, which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. This program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.

Achondroplasia is a rare genetic condition causing skeletal dysplasia and, for many affected individuals, an increased risk of muscular, neurological, and cardiorespiratory complications. YUVIWEL is a prodrug of C-type natriuretic peptide (CNP) administered once weekly, designed to provide continuous exposure of active CNP to receptors on tissues throughout the body to counteract the overactive FGFR3 signaling in achondroplasia.

The FDA based its approval of YUVIWEL on their review of the clinical package for TransCon CNP submitted with the Company's New Drug Application, which included safety and efficacy data from three randomized, double-blind, placebo-controlled clinical trials and up to three years of open-label extension data. The pivotal ApproaCH Trial data is available in JAMA Pediatrics.

Ascendis plans to offer a suite of patient services for YUVIWEL through its U.S. Ascendis Signature Access Program (A.S.A.P.), including support navigating the treatment journey and financial assistance programs for eligible patients.

The approval follows an extension of the FDA review period announced in November 2025. The FDA notified the Company that information submitted on November 5, 2025, related to the post-marketing requirement, in response to the FDA's ongoing review of the New Drug Application for TransCon CNP for children with achondroplasia, constituted a major amendment to the NDA. Accordingly, the FDA extended the PDUFA target action date by three months to February 28, 2026.

Separately, Ascendis announced topline results from Week 52 of COACH, the first Phase 2 clinical trial to evaluate combination therapy with once-weekly TransCon CNP (navepegritide) and once-weekly TransCon hGH (lonapegsomatropin) in children with achondroplasia. At Week 52, combination therapy showed durable growth without compromising safety or tolerability. In addition, combination therapy demonstrated benefits beyond linear growth with improvements in body proportionality and arm span, aligning with the increase in linear growth.

For the TransCon CNP treatment-naïve cohort, mean annualized growth velocity (AGV) was 8.80 cm/year, with an improvement in mean ACH height Z-score of +1.02 over 52 weeks, indicating a tripling of efficacy compared to TransCon CNP monotherapy. For the TransCon CNP-treated cohort (average treatment of 2.56 years), mean AGV was 8.42 cm/year, representing an increase from baseline at Week 52 of 3.28 cm/year, with an improvement in mean ACH height Z-score of +0.86, increasing from 1.28 to 2.15 over 52 weeks.

After 52 weeks, children treated with combination therapy exceeded the 97th-percentile AGV of average-stature children. Combination therapy was generally well tolerated, with generally mild treatment-emergent adverse events (TEAEs), consistent with TransCon CNP and TransCon hGH monotherapies. All children completed 52 weeks of treatment and remain on therapy in COACH as of January 2026.

COACH is an ongoing proof-of-concept prospective Phase 2 open-label trial to investigate the efficacy, safety, and tolerability of combined treatment with once-weekly TransCon CNP at 100 µg/kg/week and once-weekly TransCon hGH at a starting dose of 0.30 mg/kg/week in children with achondroplasia aged 2 to 11 years. The trial included a cohort of TransCon CNP treatment-naïve children (N=12, mean age 4.67 years) and a cohort of TransCon CNP-treated children (N=9, mean age 7.89 years), who had received TransCon CNP (100 µg/kg/week) for a mean of 2.56 years in clinical trials.