Sumitomo Pharma America has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to enzomenib (DSP-5336) for the treatment of relapsed/refractory (R/R) acute leukemia harboring a KMT2A rearrangement (KMT2Ar). Enzomenib is an investigational, oral, small molecule inhibitor of the menin–KMT2A protein interaction, a pathway implicated in leukemic cell proliferation and growth.
The designation, which is intended to expedite development and review of therapies for serious or life-threatening conditions, was supported by clinical trial evidence suggesting enzomenib may offer substantial improvement over available therapy. Specific response rate data or other numerical clinical findings underlying the designation were not disclosed in the announcement.
Key finding
The FDA granted Breakthrough Therapy designation to enzomenib for R/R KMT2A-rearranged acute leukemia, potentially accelerating its regulatory path, though no clinical efficacy or safety data were publicly disclosed to support the designation.
Study Design
| Trial | Registrational Phase 2 Horizen-1 study (NCT04988555) |
|---|---|
| Population | Adults with R/R acute leukemia with KMT2A rearrangement or NPM1 mutation |
| Treatment | Enzomenib monotherapy (oral small molecule menin–KMT2A inhibitor) |
Enzomenib is also being evaluated in combination with standard-of-care regimens in patients with newly diagnosed and R/R acute myeloid leukemia (AML) in the ongoing Phase 1/2 dose-escalation/dose-expansion study DSP-5336-101 (NCT04988555). Primary endpoints and key secondary endpoints for the Horizen-1 study were not specified in the announcement.
Results and Safety
The announcement did not disclose specific efficacy or safety data from the Horizen-1 study or any other clinical trial of enzomenib. No response rates, survival outcomes, or adverse event data were reported. In preclinical studies cited by the company, enzomenib demonstrated selective growth inhibition in human acute leukemia cell lines with KMT2A rearrangements or NPM1 mutations, and reduced expression of leukemia-associated genes HOXA9 and MEIS1 while increasing expression of the differentiation marker CD11b.
The clinical data that informed the FDA’s Breakthrough Therapy designation decision, which may include unpublished trial data per FDA program requirements, were not made available at this time.
Clinical Context
R/R KMT2Ar acute leukemia is an aggressive blood cancer characterized by rapid onset, aggressive progression, and substantially worse outcomes compared with non-KMT2Ar acute leukemias. Even with contemporary chemotherapy and hematopoietic stem cell transplantation, patients in this setting typically experience limited, short-lived responses, underscoring the unmet need for novel targeted approaches.
Enzomenib has now received multiple FDA designations, including Orphan Drug designation for AML (June 2022) and acute lymphoblastic leukemia (July 2026), Fast Track designation for R/R AML with KMT2Ar or NPM1 mutation (June 2024), and now Breakthrough Therapy designation for R/R KMT2Ar acute leukemia. Japan’s Ministry of Health, Labour and Welfare also granted orphan drug designation for the R/R AML indication in September 2024. Whether and when regulatory submissions based on Horizen-1 data may be filed has not been announced.
Sources
- Sumitomo Pharma America. “Sumitomo Pharma America Announces Enzomenib (DSP-5336) Receives FDA Breakthrough Therapy Designation for Treatment of R/R KMT2A-Rearranged Acute Leukemia.” Press release. October 26, 2026. View source.
