Cogent's Bezuclastinib Outperforms Placebo in Phase 3 Trial, Challenging Blueprint's Ayvakit

Cogent Biosciences has reported positive results from a phase 3 trial of its KIT inhibitor bezuclastinib, potentially setting the stage for a new competitor to Blueprint Medicines' Ayvakit in the treatment of systemic mastocytosis.

Trial Results and Primary Endpoint

The phase 3 trial, which enrolled 179 patients with non-advanced systemic mastocytosis, demonstrated that bezuclastinib significantly outperformed placebo in reducing total symptom scores. After 24 weeks, patients receiving bezuclastinib experienced a 24.3-point reduction in total symptom scores, compared to a 15.4-point reduction in the placebo group. The 8.91-point difference between the two arms was sufficient for the trial to meet its primary endpoint.

Cogent claims these results establish new benchmarks for both placebo-adjusted and absolute symptomatic improvement in this patient population. The trial included patients with both indolent and smoldering forms of systemic mastocytosis.

Comparison to Ayvakit

While direct comparisons between trials should be made cautiously, Cogent's results appear promising when viewed alongside data from Blueprint's Ayvakit. Blueprint's phase 3 trial, which used a different scoring system, reported a placebo-adjusted difference of 5.69 points. Cogent has argued that the scoring systems are highly analogous, potentially positioning bezuclastinib as a strong competitor in the market.

In terms of biomarker reduction, 87.4% of patients on bezuclastinib experienced a 50% or greater reduction in serum tryptase, a marker of mast cell degranulation. This compares favorably to the 54% of patients who achieved this level of reduction on Ayvakit. In both trials, no patients on placebo reached this threshold.

Safety Profile and Next Steps

The safety profile of bezuclastinib appears generally manageable, with the most common treatment-emergent adverse events being changes in hair color (69.5% of patients) and altered taste (23.7% of patients). However, 5.9% of patients discontinued treatment due to elevated liver enzymes, which fully resolved after discontinuation.

Based on these positive results, Cogent plans to file for FDA approval of bezuclastinib later this year. The company is well-positioned financially to pursue this goal, with a current cash balance of $237 million and access to up to $350 million more through a debt facility.

The announcement of these results has been well-received by investors, with Cogent's shares climbing 14% to $8.65 in premarket trading. As the company moves forward with its regulatory submission, the pharmaceutical industry will be watching closely to see how bezuclastinib may reshape the treatment landscape for systemic mastocytosis.