Ascendis' dwarfism drug boosts growth in phase 3, challenging BioMarin

Ascendis Pharma has positioned itself as a formidable contender against BioMarin’s Voxzogo by presenting phase 3 data for its growth disorder treatment that surpassed analyst expectations. The Copenhagen-based biotech company designed a trial to evaluate its once-weekly prodrug of C-type natriuretic peptide (CNP) against a placebo in 84 children suffering from achondroplasia, a form of dwarfism. Continuous CNP exposure can stimulate growth, and while BioMarin’s Voxzogo, a CNP analog, also serves this purpose, it requires daily injections.

Ascendis' TransCon CNP presents a potential challenge to Voxzogo by offering similar benefits with less frequent administration. In the phase 3 trial, children who received TransCon CNP exhibited an annualized growth velocity (AGV) of 5.89 cm/year, significantly higher than the 4.41 cm/year observed in the placebo group. This difference was statistically significant, allowing the study to meet its primary endpoint.

The trial included children aged 2 to 11 years, while BioMarin’s study involved participants aged 5 to 14 years. This age range difference complicates direct comparisons between the trials. However, Ascendis provided subgroup data for children aged 5 to 11 years. On an investor call, Ascendis CEO Jan Mikkelsen argued that cross-trial comparison was “pretty valid.” In this subgroup, the placebo-adjusted AGV was 1.78 cm/year. In BioMarin’s trial, the placebo-adjusted AGV for their entire cohort was 1.13 cm/year, but analyst Cory Kasimov from Evercore ISI noted that for the 5 to 11-year-old subgroup, BioMarin’s figure was 1.74 cm/year. Gavin Clark-Gartner, another analyst from Evercore, concluded that the efficacy of the two drugs is comparable.

Ascendis' promising results led to a 17% increase in its share price, reaching almost $140, whereas BioMarin’s stock dropped nearly 18% to below $70. Despite this, Kasimov and his team remain optimistic about Voxzogo’s market position. They emphasized that Voxzogo will have a notable head start in the U.S. market and is already approved in 44 countries. Additionally, Voxzogo has a solid safety profile, dominates the 0 to 2-year-old segment, and is under evaluation for five other skeletal conditions.

Ascendis plans to file for FDA approval in the first quarter of 2025, with European submissions following in the third quarter of the same year. The company faced setbacks with its hypoparathyroidism drug application, receiving a complete response letter and experiencing a three-month delay upon refiling. However, CEO Mikkelsen expressed confidence that the team has learned from these challenges and that the approval process for TransCon CNP will be smoother.