Bezuclastinib Shows Superior Symptomatic Improvement in Mast Cell Activation Syndrome Patients.

Bezuclastinib, a treatment for systemic mastocytosis, showed superior symptom improvement and mast cell burden reduction compared to placebo. Patients treated with bezuclastinib achieved a mean change in total symptom score of -24.3 points, compared to -15.4 points for placebo. The treatment also demonstrated a favorable safety and tolerability profile. A New Drug Application (NDA) submission to the FDA is expected by end of 2025.

Cogent Biosciences (NASDAQ: COGT) has announced significant results from its SUMMIT trial, showcasing the efficacy and safety of bezuclastinib in treating non-advanced systemic mastocytosis (NonAdvSM). The trial achieved statistically significant improvements across all primary and key secondary endpoints, positioning the company for a New Drug Application (NDA) submission to the FDA by the end of 2025.

The SUMMIT trial, a registration-directed Part 2 study, evaluated bezuclastinib versus placebo in patients with NonAdvSM. The primary endpoint, a mean change in total symptom score (TSS) at 24 weeks, demonstrated a highly statistically significant difference. Patients treated with bezuclastinib showed a mean reduction of 24.3 points in TSS compared to 15.4 points for placebo, resulting in a placebo-adjusted TSS improvement of 8.91 points (p=0.0002) [1]. This represents a substantial improvement in symptom management for patients with NonAdvSM.

One of the most compelling data points is the 87.4% response rate for patients achieving at least a 50% reduction in serum tryptase with bezuclastinib compared to 0% for placebo (p0.0001) [1]. Serum tryptase is a gold standard biomarker for mast cell burden, indicating that bezuclastinib effectively targets the underlying disease mechanism by inhibiting the KIT D816V mutation that drives mastocytosis.

The safety profile of bezuclastinib was favorable, with mostly low-grade adverse events. Hair color changes (69.5%) and taste alterations (23.7%) were the most frequent adverse events, reflecting the mechanism of KIT inhibition. The discontinuation rate due to ALT/AST elevations was 5.9%, all of which resolved completely. The serious adverse event rate was lower in the treatment arm (4.2%) compared to placebo (5.0%) [1].

Cogent Biosciences' strong financial position, with $237 million in cash and access to an additional $350 million in debt, provides substantial runway for regulatory submission and potential commercialization [1]. The company is on track to share pivotal trial results from its PEAK (GIST) and APEX (AdvSM) trials in the second half of 2025.

The upcoming investor conference call and webcast on July 7, 2025, at 8:00 a.m. ET, will provide further details on the SUMMIT trial results and the company's plans for bezuclastinib's NDA submission [2].

References:
[1] https://www.stocktitan.net/news/COGT/cogent-biosciences-announces-positive-top-line-results-achieving-wqywmmyim0ot.html
[2] https://www.globenewswire.com/news-release/2025/07/07/3110920/0/en/Cogent-Biosciences-Announces-Positive-Top-line-Results-Achieving-Statistical-Significance-Across-All-Primary-and-Key-Secondary-Endpoints-from-the-SUMMIT-Trial-of-Bezuclastinib-in-P.html