FDA Accepts Cogent Biosciences' NDA for Bezuclastinib in Advanced Systemic Mastocytosis, PDUFA Set for June 2027
核心洞察
The FDA has accepted Cogent Biosciences' New Drug Application for bezuclastinib in advanced systemic mastocytosis (搜索), with a PDUFA target action date of June 29, 2027.
The filing is supported by APEX pivotal trial data showing a 65% overall response rate by mIWG-MRT-ECNM criteria and 81% response by pure pathological response criteria.
Bezuclastinib also demonstrated durable activity with 12-month progression-free survival of 79% and 12-month overall survival of 87%, with median values not yet mature.
The U.S. Food and Drug Administration has accepted Cogent Biosciences' New Drug Application for bezuclastinib in patients with advanced systemic mastocytosis (搜索) (AdvSM), assigning a Prescription Drug User Fee Act target action date of June 29, 2027. The agency also communicated that it does not currently plan to convene an advisory committee and has not identified any potential review issues.
The NDA is supported by results from the APEX pivotal trial, which Cogent most recently presented at the 2026 European Hematology Association Congress. The company said the trial demonstrated clinically meaningful responses and evidence of disease modification in patients with AdvSM.
APEX Trial Results
As of the March 31, 2026 data cutoff, the trial's primary endpoint of response per mIWG-MRT-ECNM criteria showed a 65% overall response rate, including 57% of patients achieving complete remission, complete remission with partial recovery of hematologic parameters, or partial response as their best response. Response by pure pathological response criteria reached 81%.
Bezuclastinib also showed durable clinical activity, with a 12-month progression-free survival rate of 79% and a 12-month overall survival rate of 87%. Median progression-free and overall survival were not yet mature at the data cutoff.
"This milestone brings us one step closer to potentially delivering bezuclastinib to patients with AdvSM," said Andrew Robbins, Cogent's President and Chief Executive Officer, adding that the company is preparing for potential commercial launches later this year across multiple indications.
A KIT-Driven Disease Portfolio
AdvSM is a rare, life-threatening disease driven by abnormal mast cell proliferation, often caused by mutations in the KIT (搜索) gene. Patients may experience organ damage, severe symptoms and progressive decline, with limited treatment options available, according to the company.
Bezuclastinib is a selective tyrosine kinase inhibitor designed to potently inhibit the KIT D816V (搜索) mutation as well as other mutations in KIT (搜索) exon 17. KIT D816V is responsible for driving systemic mastocytosis (搜索), a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a cancer type with strong dependence on oncogenic KIT signaling.
Cogent is advancing bezuclastinib across three indications. The company's NDA for non-advanced systemic mastocytosis (搜索) is under FDA review with a PDUFA target action date of December 30, 2026, while the NDA for GIST is also under review with a PDUFA target action date of November 30, 2026. Cogent described these regulatory milestones as progress toward bringing bezuclastinib to patients across a broad spectrum of KIT (搜索)-driven diseases.
Expanded Access and Pipeline
Working with the FDA, Cogent has established active Expanded Access Programs for U.S. patients with systemic mastocytosis (搜索) or GIST who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib.
Beyond bezuclastinib, the company's research team is developing a portfolio of targeted therapies for genetically driven diseases, targeting mutations in ErbB2, PI3Kα, KRAS and JAK2. Cogent Biosciences is based in Waltham, Massachusetts and Boulder, Colorado.
The company also disclosed that its Compensation Committee approved inducement equity awards to nine new employees on September 10, 2026, under its 2020 Inducement Plan, in accordance with Nasdaq Listing Rule 5635(c)(4). The awards comprised options to purchase 39,300 shares of common stock and 33,600 restricted stock units in the aggregate.