FDA accepts Cogent Biosciences’ NDA for bezuclastinib in advanced systemic mastocytosis, with a PDUFA target date of June 29, 2027.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
The FDA has accepted the NDA for oral bezuclastinib, a precision therapy targeting KIT-driven disease, for adults with AdvSM. The agency has not identified potential review issues and currently does not plan to convene an advisory committee.
The regulatory milestone moves bezuclastinib into formal FDA review in a disease characterized by uncontrolled accumulation of abnormal mast cells and often associated with organ dysfunction and poor clinical outcomes.
APEX Trial Shows Responses and Durable Disease Control
The NDA is supported by results from the pivotal APEX trial (NCT04996875), which evaluated bezuclastinib in patients with AdvSM. At the March 31, 2026 data cutoff, the trial reported a 65% overall response rate according to modified International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (mIWG-MRT-ECNM) criteria.
Among patients evaluated, 57% achieved complete response (CR), complete response with partial hematologic recovery (CRh), or partial response (PR) as their best response. Using pure pathological response (PPR) criteria, the response rate reached 81%.
The durability data also showed sustained disease control. The 12-month progression-free survival rate was 79%, while the 12-month overall survival rate was 87%. Median progression-free survival and overall survival had not yet matured at the data cutoff.
These findings provide the clinical basis for the FDA filing and indicate that responses observed with bezuclastinib extended beyond initial tumor or disease burden reductions.
Targeting KIT-Driven Mastocytosis
Systemic mastocytosis results from the abnormal proliferation and accumulation of mast cells in tissues. Advanced forms can cause significant organ damage and represent a particularly serious disease subtype.
Bezuclastinib is a selective KIT inhibitor. KIT signaling plays a central role in mast-cell development and survival, and activating KIT mutations, particularly KIT D816V, occur in most patients with systemic mastocytosis. By inhibiting aberrant KIT signaling, bezuclastinib targets a key molecular driver of the disease.
The program therefore represents part of a broader precision-medicine strategy focused on KIT-driven disorders.
Regulatory Pathway Extends Across Three Indications
Cogent is pursuing bezuclastinib across AdvSM, non-advanced systemic mastocytosis (NonAdvSM), and gastrointestinal stromal tumors (GIST).
The FDA is already reviewing the company’s NDA for NonAdvSM, with a PDUFA target action date of December 30, 2026. The GIST NDA has a November 30, 2026 PDUFA target action date.
The three applications could establish separate regulatory pathways for bezuclastinib across different KIT-driven patient populations.
Expanded Access Program Remains Available
While regulatory review continues, Cogent has established Expanded Access Programs in collaboration with the FDA for eligible U.S. patients with systemic mastocytosis or GIST who may benefit from bezuclastinib, including treatment with bezuclastinib plus sunitinib in disease-specific settings.
The AdvSM NDA now enters a longer regulatory review period, with the FDA expected to complete its assessment by June 29, 2027.
Reference
Cogent Biosciences Announces FDA Acceptance of New Drug Application (NDA) for Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM), Cogent Bioscience, 15 September 2026
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis, ClinicalTrials.gov ID NCT04996875
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.