FDA Accepts Bezuclastinib NDA for Advanced Systemic Mastocytosis

The FDA has accepted the New Drug Application (NDA) for bezuclastinib in patients with advanced systemic mastocytosis (AdvSM), Cogent Biosciences announced.¹ The agency assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 29, 2027, and indicated no plans for an advisory committee meeting at this time. The NDA is supported by data from the pivotal APEX trial, presented at the 2026 European Hematology Association (EHA) Congress.²

Bezuclastinib is a selective tyrosine kinase inhibitor designed to target the KIT D816V mutation and other KIT exon 17 mutations, the drivers of AdvSM. Cogent's NDAs for bezuclastinib in nonadvanced systemic mastocytosis and gastrointestinal stromal tumors (GIST) remain under FDA review, with respective PDUFA dates of December 30, 2026, and November 30, 2026.¹ The AdvSM acceptance extends the company's regulatory momentum across 3 KIT-driven indications.

"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,” said Andrew Robbins, president and chief executive officer of Cogent Biosciences, in the news release.¹

The NDA acceptance depends on results from the APEX pivotal trial (NCT04996875) in patients with AdvSM, most recently presented at the 2026 EHA Congress.² As of the March 31, 2026, data cutoff, the primary end point of response per mIWG-MRT-ECNM criteria showed a 65% overall response rate.¹ Complete remission (CR), CR with partial hematologic recovery (CRh), or partial response (PR) as best response occurred in 57% of patients.¹

Response by pure pathological response (PPR) criteria reached 81%. Cogent's submission draws on the trial's KIT D816V-driven AdvSM population, consistent with the drug's proposed mechanism of action.¹

Bezuclastinib also demonstrated durable clinical activity in the APEX trial. The 12-month progression-free survival (PFS) rate was 79%, and the 12-month overall survival (OS) rate was 87%.¹ Median PFS and OS had not yet been reached at the time of the data cutoff.¹

Bezuclastinib Safety Profile and Regulatory Timeline

Cogent noted the FDA identified no potential review issues at this time. The agency does not currently plan to convene an advisory committee meeting on the application.¹

Beyond AdvSM, bezuclastinib carries 2 additional NDAs under FDA review. The application for nonadvanced systemic mastocytosis carries a PDUFA target action date of December 30, 2026.¹ The GIST application carries a PDUFA date of November 30, 2026.¹

Cogent has also established expanded access programs allowing eligible US patients with SM or GIST to receive bezuclastinib, alone or in combination with sunitinib, outside a clinical trial. The company said it has built a commercial and medical team in preparation for potential launches later in 2026, pending FDA action across the 3 indications.¹

For dermatology and hematology-oncology practices managing AdvSM, an approved bezuclastinib could offer another KIT-targeted option alongside existing tyrosine kinase inhibitor therapy, pending the FDA's June 2027 action date. Continued regulatory progress across the nonadvanced systemic mastocytosis and GIST indications suggests broader future application of bezuclastinib in KIT-driven diseases.¹

References

1. Cogent Biosciences announces FDA acceptance of New Drug Application (NDA) for bezuclastinib in patients with advanced systemic mastocytosis (AdvSM). News release. Cogent Biosciences. September 15, 2026. Accessed September 15, 2026. https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-announces-fda-acceptance-new-drug-1
2. Cogent Biosciences announces preclinical data from novel JAK2 V617F inhibitor at the 2026 European Hematology Association (EHA) Congress. News release. Cogent Biosciences. June 12, 2026. Accessed September 15, 2026. https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-announces-preclinical-data-novel-jak2-v617f

Frequently Asked Questions

What is bezuclastinib being evaluated for?
Bezuclastinib is under FDA review for advanced systemic mastocytosis (AdvSM), as well as nonadvanced systemic mastocytosis and gastrointestinal stromal tumors (GIST) driven by KIT exon 17 mutations.

How does bezuclastinib work?
Bezuclastinib selectively inhibits the KIT D816V mutation and other KIT exon 17 mutations that drive systemic mastocytosis and GIST.

What did the APEX trial show?
The APEX trial found a 65% overall response rate in AdvSM by mIWG-MRT-ECNM criteria, with 12-month progression-free and overall survival rates of 79% and 87%, respectively.