On November 13, 2025, the U.S. Food and Drug Administration (FDA) approved ziftomenib (Komzifti), a menin inhibitor, for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options available.
Efficacy for ziftomenib was evaluated in KO-MEN-001 (ClinicalTrials.gov identifier NCT04067336), an open-label, single, arm, multicenter trial in 112 adults with relapsed or refractory AML with an NPM1 mutation, who were 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 hematologic 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 = 0.1–41.2 months). The CR+CRh rate was 21.4% (95% confidence interval [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 and/or platelet transfusions at baseline, 14 (21.2%) became independent of red blood cell and platelet transfusions during any 56-day post-baseline period. Of the 46 patients who were independent of both red blood cell and platelet transfusions at baseline, 12 patients (26.1%) remained transfusion independent during any 56-day post-baseline period.
Prescribing information for ziftomenib includes warnings and precautions for differentiation syndrome, QTc interval prolongation, and embryo-fetal toxicity.
The recommended dose for ziftomenib is 600 mg taken orally once daily until disease progression or unacceptable toxicity.
This application was granted priority review. Ziftomenib has also been granted Breakthrough Therapy and Orphan Drug designations.
