Ascendis Reports Positive Results for Experimental Achondroplasia Therapy

Rare Daily Staff

Ascendis Pharma reported positive topline data from its pivotal double-blind placebo-controlled trial of its experimental once weekly therapy TransCon CNP in children with achondroplasia, the most common form of dwarfism.

News of the results sent shares of Ascendis up about 17 percent to $140 and shares of its competitor BioMarin down about 17 percent to $70.90 in midday trading. BioMarin makes the achondroplasia drug Voxzogo, which is dosed daily.

Achondroplasia (ACH) is caused by a genetic mutation in the fibroblast growth factor receptor 3 (FGFR3). This leads to an imbalance between the stimulatory and inhibitory signaling pathways involved in regulating bone growth. People living with ACH may experience serious complications and comorbidities due to inhibited skeletal development. Complications may include sleep apnea and respiratory problems, chronic back and leg pain from lower spine impingement, and sudden infant death from compression of the brain stem. Chronic ear infections due to eustachian tube problems can lead to hearing loss and speech delay. Children with ACH may also experience social and emotional challenges.

TransCon CNP is an experimental prodrug of C-type natriuretic peptide (CNP) in development for the treatment of ACH in children. It is designed to provide continuous CNP exposure. The goal of is to optimize efficacy with a safe and convenient once-weekly dose. TransCon CNP has orphan designation for the treatment of ACH in both the United States and Europe.

In the trial, children treated with TransCon CNP demonstrated annualized growth velocity (AGV) superior to placebo. TransCon CNP also demonstrated statistically significant improvements in other growth parameters.

“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 with a low incidence of injection-site reactions,” said Jan Mikkelsen, Ascendis Pharma’s President and CEO.

For the primary endpoint of AGV at Week 52, children treated with TransCon CNP demonstrated an LS mean AGV of 5.89 cm/year compared to 4.41 cm/year in the placebo arm, an LS mean difference of 1.49 cm/year.

TransCon CNP continues to show a safety profile comparable to placebo and was generally well-tolerated, with generally mild treatment-emergent adverse events (TEAEs), no evidence of hypotensive effect, and a low frequency of injection site reactions (0.41 events per patient year), all mild.

No adverse events (AEs) led to discontinuation of TransCon CNP or withdrawal from the trial and no serious adverse events (SAEs) were assessed as related to TransCon CNP.

As of today, all 82 children who completed the double-blind period are continuing in the open-label extension of the ApproaCH Trial.

Photo: Jan Mikkelsen, Ascendis Pharma’s president and CEO