FDA grants breakthrough therapy designation to enzomenib for R/R KMT2A-rearranged acute leukemia

On October 26, 2026, the U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to enzomenib, an oral menin inhibitor, for the treatment of patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia.¹

Enzomenib is currently being evaluated in the ongoing phase I/II Horizen-1 trial (NCT04988555) as monotherapy for the treatment of R/R KMT2Ar or NPM1-mutated (NPM1m) acute leukemias and in combination with standard of care regimens for the treatment of patients with newly diagnosed (ND) and R/R acute myeloid leukemia (AML).^1,2 Results from the Horizen-1 trial demonstrated an overall response rate (ORR) of 73.3% and a complete response (CR) / CR with partial hematologic recovery (CRh) rate of 40% among patients with KMT2Ar acute leukemia at the recommended phase II dose (n = 15).³ Among patients with NPM1m AML (n = 25), the CR/CRh rate was 44% at doses ≥200 mg; dose optimization is ongoing. The most common treatment-emergent adverse events included nausea (39.7%), vomiting (27.6%) and febrile neutropenia (27.6%); no dose-limiting toxicities were reported.³