The US Food and Drug Administration (FDA) has approved Syndax Pharmaceuticals’ Revuforj (revumenib) as the first menin inhibitor for relapsed or refractory (R/R) acute leukaemia.
The approval covers both adults and children aged one year and older with lysine methyltransferase 2A (KMT2A) gene translocations. It follows prior designations for breakthrough therapy, fast track, and priority review, with the new drug application (NDA) reviewed through the FDA’s real-time oncology review (RTOR) process.
Syndax CEO Michael Metzger said: “The approval of Revuforj is a remarkable achievement that reflects the dedication and tenacity of everyone involved, especially the patients and clinicians who participated in our trial and our talented Syndax team.
“We are well-prepared to launch Revuforj this month and we are committed to rapidly advancing the development of Revuforj across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML.”
The FDA’s approval was based on data from the Phase 1/2 AUGMENT-101 clinical trial, which involved 104 patients with R/R acute leukaemia. The trial reported a combined complete remission (CR) and CR with partial haematological recovery (CRh) rate of 21%.
The median duration of remission was 6.4 months, and 23% of patients proceeded to haematopoietic stem cell transplantation (HSCT) after treatment.
In addition to its use in patients with KMT2A translocations, Revuforj is being evaluated for treating acute myeloid leukaemia (AML) with nucleophosmin 1 (NPM1) mutations.
Trials have shown efficacy when used as a monotherapy in this population, with additional studies underway to assess its use in combination therapies for newly diagnosed and other patient groups.
Regulatory recognitions for Revuforj include orphan drug status for AML, acute lymphoblastic leukaemia, and acute leukaemias of ambiguous lineage. It has also received breakthrough therapy and fast track designations for R/R acute leukaemias involving KMT2A rearrangements or NPM1 mutations.
Safety data from trials involving 135 patients highlighted common adverse reactions, including haemorrhage, nausea, phosphate imbalances, and infections. Dose reductions were needed in 10% of patients, while 12% discontinued treatment due to adverse effects.
Syndax plans to distribute 110mg and 160mg tablets of Revuforj through speciality distributors in the US starting this month. For patients weighing less than 40kg, a 25mg tablet formulation is expected by late Q1 or early Q2 of 2025. An oral solution will be made available under an expanded access programme in the interim.
Earlier this month, Syndax entered into a synthetic royalty agreement with Royalty Pharma, tied to US net sales of Niktimvo (axatilimab-csfr). As part of the deal, Syndax received a $350m upfront payment in exchange for a 13.8% royalty on the drug’s net sales in the US.
