Ascendis Pharma has emerged as a potential threat to BioMarin’s Voxzogo, reporting phase 3 growth disorder data that exceeded analyst expectations and position the biotech to file for approval next year.
Copenhagen-based Ascendis designed the trial to compare its once-weekly prodrug of C-type natriuretic peptide (CNP) to placebo in 84 children with the dwarfism condition achondroplasia. Providing children with continuous exposure to CNP can accelerate growth. BioMarin serves that need with its CNP analog Voxzogo—the centerpiece of its growth strategy—but that drug needs to be injected once a day.
Ascendis’ TransCon CNP could challenge Voxzogo. In the phase 3 study, the biotech saw an annualized growth velocity (AGV) of 5.89 cm/year in the 57 children who received TransCon CNP compared to 4.41 cm/year in the 27-subject placebo arm. The difference was statistically significant, causing the trial to hit its primary endpoint.
The study enrolled children aged 2 to 11 years. Participants in BioMarin’s study ranged in age from 5 to 14 years. While that difference complicates cross-trial comparisons, Ascendis included subgroup data on patients aged 5 to 11 years. Ascendis CEO Jan Mikkelsen said he believes cross-trial comparison is “pretty valid” on a call with investors to discuss the data.
Placebo-adjusted AGV was 1.78 cm/year in the subgroup. While BioMarin’s phase 3 trial included older children, and reported a placebo-adjusted AGV of 1.13 cm/year, Evercore ISI analyst Cory Kasimov said the figure for Voxzogo in children aged 5 to 11 years was 1.74 cm/year. The comparison supports the conclusion of Gavin Clark-Gartner, Kasimov’s Evercore colleague, that the drugs’ efficacy is in the same ballpark.
Ascendis’ share price rose 17% to almost $140 in the wake of the data drop. Meanwhile, BioMarin’s stock fell almost 18% to below $70. Yet, Kasimov and his team continue to believe in BioMarin’s vision for its CNP analog.
“Our view on Voxzogo’s positioning remains [unchanged], and we still think our model is conservative,” Kasimov said. “The product will have at least a 4+ year head start in the U.S. (also approved in 44 countries total), has a robust safety profile, will own the 0- to 2-year-old segment (at least initially), and is being evaluated in five other skeletal indications,” they said in a note.
Ascendis plans to file for FDA approval in the first quarter of 2025 and submit the paperwork in Europe in the third quarter of that year. The biotech ran into problems when applying for approval of its hypoparathyroidism drug, receiving a complete response letter and facing a three-month delay when it refiled, but Mikkelsen said the team has learned from the experience and TransCon CNP is “much more simple.”