Ziftomenib: First Approval.

Ziftomenib (KOMZIFTI) is an oral, selective, once-daily menin inhibitor in development by Kura Oncology for the treatment of NPM1-mutated (NPM1-m) or KMT2A-rearranged (KMT2A-r) acute myeloid leukaemia (AML), KMT2A-r acute lymphoblastic leukaemia and gastrointestinal stromal tumours (GIST). The menin-KMT2A complex and mutated NPM1 proteins co-occupy specific gene promoter sites and increase transcription of leukaemogenic genes. By blocking the interaction between menin and KMT2A, ziftomenib downregulates transcription of key leukaemogenic factors and restores differentiation pathways to exert anti-leukaemic effects in NPM1-m and KMT2A-r AML. Ziftomenib received its first approval on 13 Nov 2025 in the USA for the treatment of adults with relapsed or refractory AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options. This article summarises the milestones in the development of ziftomenib leading to this first approval for relapsed or refractory AML associated with an NPM1 mutation.