Pivotal TransCon™ CNP Trial Meets Primary Objective, Shows AGV Superiority Over Placebo

Ascendis Pharma A/S has announced the topline results from the pivotal ApproaCH Trial, which evaluated TransCon CNP (navepegritide) in children with achondroplasia. The trial, conducted in a double-blind, placebo-controlled manner, included 84 children aged 2-11 years who were randomized in a 2:1 ratio to receive either TransCon CNP or a placebo.

TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP), designed to be administered once weekly for sustained release and continuous exposure of active CNP. The results from the trial revealed that children treated with TransCon CNP demonstrated an annualized growth velocity (AGV) that was significantly superior to those who received the placebo. Other growth parameters, including height Z-score and change from baseline AGV, also showed significant improvements with TransCon CNP.

Dr. Ravi Savarirayan from the Murdoch Children’s Research Center in Australia, who is also an investigator in the trial, remarked on the efficacy, safety, tolerability, and convenience of the once-weekly TransCon CNP treatment. He expressed optimism about the potential of TransCon CNP to provide a new treatment option that could reduce injection frequency, improve compliance, and ease the burden on caregivers.

Jan Mikkelsen, President and CEO of Ascendis Pharma, highlighted that children treated with TransCon CNP not only outpaced the growth rates of the general population but also achieved this with safety and tolerability similar to the placebo group. He emphasized that TransCon CNP, along with SKYTROFA®, positions Ascendis as a leader in treating skeletal dysplasias and growth disorders.

The trial's primary endpoint was the change in AGV from baseline, which was met successfully. Secondary and other selected endpoints also supported the notion that TransCon CNP might provide benefits beyond just linear growth. The safety summary indicated that TransCon CNP was generally well-tolerated, with a low frequency of mild injection site reactions.

All 82 children who completed the double-blind period of the trial have continued into an open-label extension. Dr. Aimee Shu, Senior Vice President of Clinical Development, Endocrine & Rare Disease at Ascendis, expressed gratitude to the study participants, their families, and the clinical investigators. She reiterated the company's commitment to advancing TransCon CNP as a potential new treatment option for children with achondroplasia.

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 Authorization Application (MAA) to the European Medicines Agency in the third quarter of 2025 for the treatment of children with achondroplasia.

The ApproaCH Trial is a pivotal, multicenter study involving children aged 2-11 years with achondroplasia. Participants were randomized to receive either TransCon CNP at a dose of 100μg/kg/week or a placebo for 52 weeks during the double-blind period. Following this, all participants had the option to continue receiving TransCon CNP in an open-label extension phase.

Ascendis Pharma is dedicated to developing new and potentially best-in-class therapies using its TransCon technology platform. The company aims to make a significant difference in patients' lives and operates with core values centered around patients, science, and passion. Ascendis Pharma is headquartered in Copenhagen, Denmark, with additional facilities in Europe and the United States.