Cogent challenges Blueprint Medicines’ Ayvakit with strong trial data for rare immune disease

Cogent Biosciences' bezuclastinib met key goals in a mid-stage trial for systemic mastocytosis, reducing symptoms and key biomarkers compared to placebo.

Why it matters: The results position bezuclastinib as a strong competitor to the market-leading Ayvakit, developed by Blueprint Medicines, and bring Cogent closer to FDA approval for a rare but disruptive immune condition.

Backstory: Systemic mastocytosis causes excessive mast cell buildup in the body, triggering symptoms like pain, fatigue, and allergic reactions. Current treatment options are limited, with Ayvakit being the only FDA-approved drug, but some clinicians report needing to increase doses for better results.

Big picture: Bezuclastinib’s efficacy and favorable safety profile could reshape the treatment landscape for both advanced and non-advanced forms of systemic mastocytosis. This is a pivotal moment for Cogent, and a potential blow to the $9.5 billion acquisition of Blueprint by Sanofi last month, given that Ayvakit was the main asset behind the deal.

The trial in detail: In the Phase 2 “Summit” trial, Cogent enrolled about 180 patients with non-advanced systemic mastocytosis. Those treated with bezuclastinib reported an average reduction of 24.2 points in symptom scores over six months, compared to 15.4 points in the placebo group. 87.4% of patients receiving bezuclastinib experienced a reduction of at least 50% in serum tryptase levels — a protein secreted by mast cells — while no placebo recipients showed similar improvement.

What’s next: the FDA filing is expected later in 2025; Cogent is also running trials in advanced mastocytosis and gastrointestinal tumors. Cogent’s stock surged up to 30% on data release.