Bezuclastinib Meets Primary Endpoint in Phase 3 Trial for Systemic Mastocytosis

Cogent Biosciences has announced that its Phase 3 trial for bezuclastinib met the primary endpoint, setting the stage for a potential FDA submission. The investigational KIT inhibitor is being developed for patients with non-advanced systemic mastocytosis, a group that includes individuals with indolent and smoldering forms of the disease.

The study enrolled 179 participants who were randomly assigned to receive either bezuclastinib or a placebo. After 24 weeks of treatment, patients receiving bezuclastinib saw a 24.3-point reduction in total symptom scores, compared to a 15.4-point reduction among those on placebo. The placebo-adjusted difference of 8.91 points was sufficient for the trial to meet its primary endpoint.
Cogent stated that the trial established new benchmarks for both absolute and placebo-adjusted symptom improvements in this patient population. The current treatment available for indolent systemic mastocytosis is Blueprint Medicines’ Ayvakit, which was evaluated in a separate Phase 3 trial using a different symptom scoring system. Cogent has argued that the two scoring methods are highly analogous and reported that the results were nearly identical when both were used in the earlier part of its study. In Blueprint’s trial, the placebo-adjusted difference using its scoring method was 5.69 points.
Data on patients achieving a 50% or greater symptom improvement was not included in Cogent’s press release. For comparison, Blueprint reported that 25% of patients on Ayvakit reached this level of improvement, versus 10% for placebo.
In terms of biomarker response, Cogent reported that 87.4% of patients treated with bezuclastinib had a 50% or greater reduction in serum tryptase, a marker of mast cell degranulation. In Blueprint’s trial, 54% of patients receiving Ayvakit experienced the same level of reduction. No patient in the placebo arm of either trial achieved a 50% or greater decrease in serum tryptase.

Adverse events were reported in both studies. In the Cogent trial, nearly 6% of patients discontinued bezuclastinib due to elevated liver enzymes, which fully resolved. The most frequent treatment-emergent adverse events were hair color changes, observed in 69.5% of patients, and altered taste, reported by 23.7%. In Blueprint’s study, one patient permanently discontinued Ayvakit due to an adverse reaction.
Cogent plans to seek FDA approval for bezuclastinib within the year. The company reported a cash balance of $237 million and stated that it has access to an additional $350 million through a debt facility. Following the announcement, shares in Cogent rose 14% to $8.65 in premarket trading.