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FDA Approves Ziftomenib, First Menin Inhibitor, for NPM1-Mutant Relapsed AML

The once-daily Komzifti won clearance on early-phase data showing meaningful remissions in a refractory molecular subset despite substantial toxicity that will require careful monitoring.

Overview

  • The authorization covers adults with relapsed or refractory acute myeloid leukemia harboring a susceptible NPM1 mutation who lack satisfactory alternative options.
  • In the KOMET-001 analysis, complete remission plus CR with partial or full hematologic recovery was 21.4% at a median 4.2 months of follow-up, with a median duration of five months.
  • In phase 2 (n=92), the complete remission rate was 14% and CRh was 9% for a combined 23%, with 63% of responders achieving minimal residual disease negativity.
  • Safety findings showed treatment-emergent adverse events in all patients and grade 3 or higher events in 93%, including differentiation syndrome, anemia, febrile neutropenia, thrombocytopenia, and pneumonia, with 3% discontinuing due to drug-related adverse events.
  • The recommended dose is 600 mg once daily until progression or unacceptable toxicity, and labeling includes warnings for differentiation syndrome, heart rhythm changes, and potential harm to unborn babies; the NPM1 mutation occurs in roughly 30% of AML cases.