A phase 3 trial of Cogent Biosciences’ bezuclastinib has hit its primary endpoint, teeing the biotech up to seek FDA approval for a potential rival to Blueprint Medicines’ Ayvakit.
Cogent randomized 179 patients with non-advanced systemic mastocytosis to receive the KIT inhibitor bezuclastinib or placebo. After 24 weeks, total symptom scores fell 24.3 points on bezuclastinib and 15.4 points on placebo. The 8.91-point difference between the two arms was big enough for the trial to hit its primary endpoint.
The biotech said the trial established new benchmarks for placebo-adjusted and absolute symptomatic improvement for the patient population. Blueprint’s Ayvakit is the current treatment for patients with indolent systemic mastocytosis. Cogent’s trial enrolled people with indolent or smoldering forms of the disease.
Blueprint used a different scoring system than Cogent as the primary endpoint of its phase 3 trial. However, Cogent has argued (PDF) that the scales are highly analogous and showed the results for the two scoring systems were nearly identical in the first part of its study. Blueprint reported (PDF) a placebo-adjusted difference of 5.69 points on its scoring system.
One-quarter of patients on Ayvakit had a 50% or greater improvement in symptoms, compared to 10% of their peers on placebo. Cogent’s press release lacks comparable data for bezuclastinib, with the biotech only providing a statistically significant p value for the secondary endpoint.
Almost 54% of patients on Ayvakit had a 50% or greater reduction in serum tryptase, a marker of mast cell degranulation. Cogent said 87.4% of patients on bezuclastinib experienced such a reduction. Nobody on placebo in either trial had a 50% or greater reduction in the biomarker.
Almost 6% of patients on bezuclastinib stopped treatment because of elevated liver enzymes that fully resolved. The most common treatment-emergent adverse events on the study drug were changes in hair color and altered taste, which affected 69.5% and 23.7% of patients, respectively. One person permanently stopped taking Ayvakit in Blueprint’s trial because of an adverse reaction.
Cogent plans to file for FDA approval of bezuclastinib this year. The biotech has a current cash balance of $237 million and access to up to $350 million more via a debt facility. Shares in Cogent climbed 14% to $8.65 in premarket trading.