FDA

Komzifti OK’d for relapsed or refractory AML with NPM1 mutation

November 18, 2025

Brand name: Komzifti

Generic name: ziftomenib

Manufacturer: Kura Oncology

Approval date: November 13, 2025

FDA has approved Komzifti (ziftomenib), 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.

Efficacy

Efficacy was evaluated in KO-MEN-001 (NCT04067336), an open-label, single, arm, multicenter trial involving 112 adults with relapsed or refractory AML with an NPM1 mutation identified using next-generation sequencing or PCR. 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. Median follow-up was 4.2 months (range, 0.1 to 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). 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 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.

Safety

The most common adverse reactions (≥20%) in the clinical trial were infection without an identified pathogen, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increase.

The most common laboratory abnormalities (≥10%) were AST increased, potassium decreased, albumin decreased, ALT increased, sodium decreased, creatinine increased, alkaline phosphatase increased, bilirubin increased, and potassium increased.

The prescribing information includes warnings and precautions for differentiation syndrome, QTc interval prolongation, and embryo-fetal toxicity.

Recommended dose

The recommended dosage of ziftomenib is 600 mg taken orally once daily until disease progression or unacceptable toxicity.

Sources:

FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation

Kura Oncology and Kyowa Kirin announce FDA approval of Komzifti™ (ziftomenib), the first and only once-daily targeted therapy for adults with relapsed for refractory NPM1-mutated acute myeloid leukemia. [News release]. 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-fda-approval-komziftitm

Komzifti (ziftomenib) [package insert]. Kura Oncology. https://kuraoncology.com/wp-content/uploads/prescribinginformation.pdf Revised November 2025. Accessed November 17, 2025.