The US Food and Drug Administration’s (FDA) acceptance of Cogent Biosciences' new drug application for bezuclastinib in adults with advanced systemic mastocytosis (AdvSM) has been announced, based on pivotal APEX trial data, with a set Prescription Drug User Fee Act (PDUFA) target action date of June 29, 2027.¹
The agency has not indicated plans for an advisory committee meeting and has not identified outstanding review issues at this stage.¹ Acceptance follows 2 other pending bezuclastinib filings, with PDUFA dates of November 30, 2026, for gastrointestinal stromal tumors (GIST) and December 30, 2026, for non-advanced systemic mastocytosis.¹ All three applications target diseases driven by mutations in KIT exon 17, including the KIT D816V mutation central to systemic mastocytosis.¹
"With the FDA's acceptance of our NDA in Advanced Systemic Mastocytosis, we have reached another important regulatory milestone for bezuclastinib and are one step closer to potentially bringing this therapy to patients with AdvSM," Andrew Robbins, president and chief executive officer of Cogent Biosciences, said in a statement. "With an excellent commercial and medical team in place, we are excited and ready for the potential launches later this year."
Bezuclastinib Efficacy Data from APEX Trial in AdvSM
The NDA rests on results from the APEX pivotal trial, most recently updated at the 2026 European Hematology Association Congress.² As of a March 31, 2026 data cutoff, bezuclastinib met its primary endpoint, response per modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis criteria, with an overall response rate of 65%.¹ Of these responses, 57% of patients achieved complete remission, complete remission with partial hematologic recovery, or partial remission as their best response.¹
Response measured by pure pathological response criteria reached 81%.¹ Cogent also reported 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 had not yet been reached at the data cutoff, reflecting ongoing follow-up across the trial population.¹
Bezuclastinib Mechanism and Access Across KIT-Driven Disease
Bezuclastinib is a selective tyrosine kinase inhibitor designed to potently inhibit the KIT D816V mutation responsible for systemic mastocytosis, along with other KIT exon 17 mutations found in GIST.¹ Cogent has established expanded access programs allowing eligible United States patients with systemic mastocytosis or GIST to receive bezuclastinib, or a combination of bezuclastinib and sunitinib, outside a clinical trial while the NDAs remain under review.¹
Cogent's pipeline beyond KIT-driven disease includes earlier-stage targeted therapy programs directed at mutations in ErbB2, PI3K-alpha, KRAS, and JAK2.¹ The company has previously characterized bezuclastinib's safety profile in the APEX trial as well tolerated, consistent with its earlier reporting on the program.² Cogent has said it expects to be positioned for potential commercial launches of bezuclastinib later in 2026, pending FDA decisions across its three pending applications.¹
If approved across all three indications, bezuclastinib would give Cogent a KIT-targeted therapy spanning systemic mastocytosis and GIST, 2 distinct diseases with limited existing options aimed specifically at KIT-driven biology.¹
Editor’s note: This piece has been edited for grammar and clarity using artificial intelligence tools.
References
Cogent Biosciences, Inc. APEX pivotal trial data in advanced systemic mastocytosis. Presented at: European Hematology Association (EHA) 2026 Congress.
