The FDA has granted Breakthrough Therapy designation to Sumitomo Pharma America’s investigational drug enzomenib (DSP-5336) for patients with relapsed or refractory acute leukemia characterized by KMT2A rearrangements. Enzomenib is an oral small-molecule inhibitor designed to disrupt the interaction between menin and KMT2A, a molecular mechanism involved in the growth and progression of certain leukemias. The designation is intended to support the development of therapies for serious conditions when clinical evidence suggests they may offer a substantial improvement over available treatments on clinically significant endpoints.

Sumitomo Pharma America is evaluating enzomenib as a single-agent treatment in the Phase 2 Horizen-1 study, which includes patients with relapsed or refractory acute leukemia involving KMT2A rearrangements or mutations in the NPM1 gene. The company is also investigating the drug in combination with standard-of-care regimens for newly diagnosed and relapsed or refractory acute myeloid leukemia in an ongoing Phase 1/2 clinical trial.

“Patients with R/R KMT2A-rearranged acute leukemia continue to face poor outcomes,” says Tsutomu Nakagawa, President and CEO of Sumitomo Pharma America. He said the designation could facilitate closer engagement with the FDA as the company works to advance the clinical program.

KMT2A-rearranged acute leukemia is an aggressive blood cancer associated with rapid progression and a poor prognosis. Patients whose disease returns after treatment or fails to respond to standard chemotherapy have limited options, and outcomes can remain poor even with hematopoietic stem cell transplantation.

The FDA previously granted enzomenib Fast Track designation in June 2024 for relapsed or refractory acute myeloid leukemia with KMT2A rearrangements or NPM1 mutations. The agency also awarded the drug orphan drug designation for acute myeloid leukemia in June 2022 and acute lymphoblastic leukemia in July 2026. Japan’s Ministry of Health, Labour and Welfare granted orphan drug designation for the relevant relapsed or refractory acute myeloid leukemia population in September 2024.

Preclinical studies have indicated that enzomenib can inhibit the growth of human acute leukemia cell lines carrying KMT2A rearrangements or NPM1 mutations. Researchers have also observed reduced expression of leukemia-associated genes HOXA9 and MEIS1, alongside increased expression of CD11b, a marker associated with cellular differentiation. These findings provide a rationale for further clinical investigation, although the drug’s safety and efficacy remain under evaluation.

Sumitomo Pharma said the Breakthrough Therapy designation will enable additional interaction with the FDA during development. The company aims to advance enzomenib as a potential treatment for patients with these high-risk forms of leukemia, for whom effective treatment options remain limited.

For more information, visit www.us.sumitomo-pharma.com.