Ziftomenib: First Approval

DeclarationsFunding The preparation of this review was not supported by any external funding.Authorship and Conflict of interest During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Aisling McGuigan is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability Not applicable.Additional information about this Adis Drug Review can be found here.AbstractZiftomenib (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.© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2026