Ascendis Pharma announced positive topline results from its pivotal ApproaCH trial, revealing that TransCon CNP (navepegritide) significantly improved annualized growth velocity (AGV) in children with achondroplasia compared to placebo. The study, involving 84 children aged 2-11 years, demonstrated a statistically significant difference in AGV, marking a potential advancement in treating this growth disorder.
The ApproaCH trial's primary endpoint was met with a least squares (LS) mean AGV difference of 1.49 cm/year (p<0.0001) at Week 52 between the TransCon CNP group (5.89 cm/year) and the placebo group (4.41 cm/year). Notably, a subgroup analysis of children aged 5-11 years showed an even more pronounced LS mean treatment difference of 1.78 cm/year (p<0.0001), indicating a greater response in this age range.
Secondary Endpoint Improvements
Beyond the primary endpoint, TransCon CNP also demonstrated statistically significant improvements in key secondary endpoints. The change in ACH Height Z-score showed an LS mean difference of 0.28 (p<0.0001) between the treatment and placebo groups. Additionally, the change in CDC Height Z-score revealed an LS mean difference of 0.30 (p=0.0003), further supporting the drug's efficacy in promoting linear growth.
Safety and Tolerability
TransCon CNP exhibited a safety profile comparable to placebo, with a low frequency of mild injection site reactions (0.41 events per patient year). No adverse events led to discontinuation of the drug or withdrawal from the trial, and no serious adverse events were assessed as related to TransCon CNP, underscoring its favorable tolerability.
Quality of Life Measures
While not statistically significant across all measures, treatment with TransCon CNP resulted in numerical improvements in health-related quality of life compared to placebo, as measured by several Achondroplasia Child Experience Measure (ACEM) domains. Predefined subgroup analyses of ACEM-Physical Functioning demonstrated potential treatment effects, supported by muscle functionality test results.
Regulatory Pathway
Ascendis Pharma plans to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) in the first quarter of 2025 and a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) in the third quarter of 2025 for TransCon CNP in the treatment of children with achondroplasia.
Expert Commentary
"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 (Australia) and an investigator in the ApproaCH Trial. "I am excited about the possibilities TransCon CNP presents for a potential new treatment option for these children that will allow decreased injection frequency, improved compliance, and reduced caregiver burden."
