Ascendis Pharma A/S announced positive topline results from its pivotal ApproaCH trial, evaluating TransCon CNP (navepegritide) in children with achondroplasia. The double-blind, placebo-controlled study demonstrated that TransCon CNP significantly improved annualized growth velocity (AGV) compared to placebo after 52 weeks of treatment.
The ApproaCH trial included 84 children aged 2-11 years, randomized in a 2:1 ratio to receive either TransCon CNP or placebo. TransCon CNP, a once-weekly investigational prodrug of C-type natriuretic peptide (CNP), is designed to provide sustained CNP exposure. The primary endpoint was AGV at Week 52.
Primary Endpoint Achieved
TransCon CNP-treated children (n=57) exhibited an LS mean AGV of 5.89 cm/year, compared to 4.41 cm/year in the placebo group (n=27), resulting in a statistically significant LS mean difference of 1.49 cm/year (p<0.0001).
Subgroup analysis of children aged 5-11 years showed an even greater difference, with TransCon CNP (n=36) demonstrating an LS mean AGV of 5.79 cm/year versus 4.02 cm/year for placebo (n=17), an LS mean difference of 1.78 cm/year (p<0.0001).
Secondary Endpoint Results
The trial also assessed secondary endpoints, including changes in height Z-scores. Children treated with TransCon CNP (n=57) showed an LS mean change from baseline ACH Height Z-score of 0.30, compared to 0.01 in the placebo arm (n=27), an LS mean difference of 0.28 (p<0.0001). For the change in CDC Height Z-score, the TransCon CNP group (n=55) demonstrated an LS mean change from baseline of 0.15, compared to -0.15 in the placebo group (n=27), an LS mean difference of 0.30 (p=0.0003).
Safety and Tolerability
TransCon CNP demonstrated a safety profile comparable to placebo and was generally well-tolerated. The frequency of injection site reactions was low (0.41 events per patient year), and all reactions were mild. No adverse events led to discontinuation of TransCon CNP or withdrawal from the trial, and no serious adverse events were assessed as related to TransCon CNP.
Implications and Future Steps
"Results of this pivotal trial demonstrate that once-weekly TransCon CNP can, if approved, address the need for an efficacious, safe, tolerable, and convenient treatment for children with achondroplasia," said Ravi Savarirayan, M.D., at the Murdoch Children’s Research Center. Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer, added, "TransCon CNP-treated children with achondroplasia exceeded the growth rate of the general population, suggesting that once-weekly TransCon CNP provides catch-up growth with safety and tolerability results comparable to placebo."
Ascendis Pharma plans to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration for TransCon CNP in the first quarter of 2025 and a Marketing Authorisation Application (MAA) to the European Medicines Agency in the third quarter of 2025.
