FDA Approves Ziftomenib for Patients With Relapsed/Refractory NPM1-Mutated Acute Myeloid Leukemia

On November 13, 2025, the US Food and Drug Administration (FDA) approved ziftomenib, a menin inhibitor, for adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have a susceptible nucleophosmin 1 (NPM1) mutation and have no satisfactory alternative treatment options.

Approval was based on results from KO-MEN-001 (NCT04067336), an open-label, single-arm, multicenter trial that enrolled 112 adults with R/R AML and an NPM1 mutation confirmed by next-generation sequencing or polymerase chain reaction. Eligible mutations included NPM1 Type A, B, and D variants as well as other mutations predicted to result in cytoplasmic localization of the NPM1 protein. Efficacy was determined by the rates of complete remission (CR), CR with partial hematologic recovery (CRh), duration of CR+CRh, and conversion from transfusion dependence to transfusion independence. 

At a median follow up of 4.2 months (range, 0.1 to 41.2), the CR rate was 17% (95% confidence interval [CI], 10.5 to 25.2), and the CRh rate was 4.5% (95% CI, 1.5 to 10.1). The CR+CRh rate was 21.4% (95% CI, 14.2 to 30.2), with a median CR+CRh duration of 5 months (95% CI, 1.9 to 8.1). 

Among 66 patients who were red blood cell (RBC) and/or platelet transfusion dependent at baseline, 21.2% became transfusion independent during any 56-day post-baseline period. Of the 46 patients who were transfusion independent at baseline, 26.1% remained transfusion independent during any 56-day post-baseline period.

The prescribing information includes warnings and precautions for differentiation syndrome, QTc interval prolongation, and embryo-fetal toxicity. The recommended dose of ziftomenib is 600 mg orally once daily, continued until disease progression or unacceptable toxicity. 

Source:

US Food and Drug Administration. Accessed November 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation