On November 13, 2025, the Food and Drug Administration approved ziftomenib (Komzifti, Kura Oncology, Inc.), a menin inhibitor, for adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation who have no satisfactory alternative treatment options.
Full prescribing information for Komzifti will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in KO-MEN-001 (NCT04067336), an open-label, single, arm, multicenter trial in 112 adults with relapsed or refractory AML with an NPM1 mutation identified using next-generation sequencing or polymerase chain reaction. Patients with NPM1 mutations, including Type A, B, and D mutations and other NPM1 mutations likely to result in cytoplasmic localization of the NPM1 protein, were enrolled.
Efficacy was established based on the rate of complete remission (CR) plus CR with partial hematological recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. The median follow-up was 4.2 months (range, 0.1 to 41.2 months). The CR+CRh rate was 21.4% (95% CI: 14.2, 30.2) and the duration of CR+CRh was 5 months (95% CI: 1.9, 8.1). The CR rate was 17.0% (95% CI: 10.5, 25.2), and the CRh rate was 4.5% (95% CI: 1.5, 10.1). Among the 66 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 14 (21.2%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 46 patients who were independent of both RBC and platelet transfusions at baseline, 12 (26.1%) patients 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.
Recommended Dosage
The recommended ziftomenib dose is 600 mg taken orally once daily until disease progression or unacceptable toxicity.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. Ziftomenib received breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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