U.S. FDA grants Breakthrough Therapy Designation for ziftomenib

On April 22, 2024, the U.S. Food and Drug Administration granted Breakthrough Drug Designation to ziftomenib, a novel therapy that targets the menin-KMT2A/MLL protein-protein interaction, for the treatment of NPM1-mutated relapsed/refractory acute myeloid leukemia. Ziftomenib received an Orphan Drug Designation from the U.S. Food and Drug Administration in July 2019.

This breakthrough drug designation was based on findings from the ongoing phase II KOMET-001 trial (NCT04067336). An acceptable safety and tolerability profile was shown in the phase I portion of the study, with most adverse events being consistent in those associated with underlying disease. Complete remission was observed in 35% of patients at the recommended phase II dose of 600 mg.

Ziftomenib is also being investigated in combination with other therapies, including venetoclax and azacitidine, 7+3 chemotherapy, gilteritinib, FLAG-Ida (fludarabine, cytarabine, granulocyte-colony stimulating factor, and idarubicin), and low-dose cytarabine in NPM1-mutant and KMT2A-rearranged newly diagnosed and relapsed/refractory acute myeloid leukemia, in the KOMET-007 (NCT05735184) and KOMET-008 (NCT06001788) trials.