Ascendis Pharma announces interim analysis results from COACH trial

Ascendis Pharma (ASND) announced Week 26 interim analysis results from its ongoing COACH Trial, the first clinical trial to evaluate combination treatment with once-weekly investigational TransCon CNP and once-weekly TransCon hGH in children with achondroplasia. Results demonstrated that TransCon hGH boosted treatment benefits of TransCon CNP, resulting in significant growth and proportionality improvements in children with achondroplasia after 26 weeks of combination treatment, with a safety and tolerability profile consistent with those observed for TransCon hGH and TransCon CNP monotherapies. TransCon CNP, which is under priority review as a monotherapy for children with achondroplasia by the U.S. Food & Drug Administration, is an investigational prodrug of C-type natriuretic peptide administered once weekly, providing continuous exposure of active CNP to receptors on tissues throughout the body, including growth plates and skeletal muscle. TransCon hGH is a prodrug of somatropin administered once weekly, providing sustained release of active, unmodified somatropin. TransCon hGH is approved and marketed as SKYTROFA for the treatment of pediatric growth hormone deficiency and is in development for other indications. The COACH Trial 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 microgram/kg/week and once-weekly TransCon hGH at 0.30 mg/kg/week in children with achondroplasia aged 2 to 11 years. The trial included a cohort of TransCon CNP treatment naive children and a cohort of TransCon CNP-treated children who had received TransCon CNP for a mean of 2.56 years in clinical trials. The trial population is representative of children with achondroplasia, except for the observed growth benefit in the TransCon CNP-treated cohort. The interim analysis will be followed by Week 52 data, expected in Q4 2025, and Ascendis plans to initiate a Phase 3 trial in Q4 2025. For TransCon CNP treatment-naive children, mean annualized growth velocity was 9.14 cm/year, representing an increase from baseline at Week 26 of 4.23 cm/year, with an improvement in mean ACH height Z-score of +0.53 over 26 weeks. For TransCon CNP-treated children, mean AGV was 8.25 cm/year, representing an increase from baseline at Week 26 of 3.10 cm/year, with an improvement in mean ACH height Z-score of +0.44 over 26 weeks. Mean AGV with TransCon CNP and TransCon hGH combination treatment exceeded the 97th percentile of average-stature children. Children treated with TransCon hGH and TransCon CNP demonstrated accelerated improvement in body proportionality at Week 26, aligning with the increase in linear growth. Bone age advanced in line with chronologic age. Safety and tolerability data were consistent with those observed for TransCon hGH and TransCon CNP monotherapies; combination treatment was generally well tolerated, with generally mild TEAEs.