FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation

The FDA approved ziftomenib (Komzifti), a menin inhibitor, on Nov 13, 2025, for adults with relapsed or refractory AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options. The decision was supported by the open-label, single-arm KO-MEN-001 trial (N=112). The primary efficacy basis included CR+CRh rate (21.4%; median duration 5 months) and transfusion independence outcomes. Label warnings include differentiation syndrome, QTc prolongation, and embryo-fetal toxicity.

Regulatory approval (FDA)

On November 13, 2025, the US Food and Drug Administration (FDA) approved ziftomenib (Komzifti; Kura Oncology, Inc.), a menin inhibitor, for adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options.

Supporting evidence

Efficacy and safety were evaluated in KO-MEN-001 (NCT04067336), an open-label, single-arm, multicenter trial in 112 adults with relapsed/refractory AML with an NPM1 mutation identified by next-generation sequencing or PCR. Enrolled mutations included Type A, B, and D and other NPM1 mutations likely to result in cytoplasmic localization of the NPM1 protein.

With median follow-up 4.2 months (range 0.1–41.2), efficacy was established based on CR+CRh rate, duration of CR+CRh, and conversion from transfusion dependence to independence:

  • CR+CRh: 21.4% (95% CI 14.2–30.2); median duration 5 months (95% CI 1.9–8.1)
  • CR: 17.0% (95% CI 10.5–25.2); CRh: 4.5% (95% CI 1.5–10.1)
  • Among 66 transfusion-dependent at baseline, 14 (21.2%) became RBC and platelet transfusion independent during any 56-day post-baseline period.

Label and dosing

Warnings/precautions include differentiation syndrome, QTc interval prolongation, and embryo-fetal toxicity. Recommended dose: 600 mg orally once daily until progression or unacceptable toxicity.

The application received priority review and had breakthrough and orphan drug designations.

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