Revuforj gets FDA priority review for AML with NPM1 mutations
Status applies to patients with relapsed, refractory disease
U.S. regulators have granted priority review to Syndax’s application to extend the approval of Revuforj (revumenib) to treat relapsed or refractory acute myeloid leukemia (AML) in patients with NPM1 gene mutations.
Revuforj is approved for certain hard-to-treat leukemias related to translocation mutations, a type of DNA rearrangement, in the KMT2A gene. Syndax’s supplemental new drug application for Revuforj included data from the Phase 1/2 AUGMENT-101 clinical trial (NCT04065399) demonstrating safety and efficacy in participants with NPM1-associated AML, a difficult-to-treat blood cancer. There aren’t any FDA-approved blood cancer treatments specifically for AML related to NPM1 mutations.
The filing “builds on the initial approval of Revuforj for [relapsed or refractory] acute leukemia with a KMT2A translocation in 2024,” Michael A. Metzger, CEO of Syndax, said in a company press release.
By granting priority review, the Food and Drug Administration (FDA) shortened the timeline for potential approval, with a decision expected Oct. 25. Priority review status is for medications that may significantly improve safety or efficacy of treatment for serious conditions.
Mutations in the NPM1 gene are found in about 28% of adults with newly diagnosed AML. These mutations cause leukemia by disrupting normal blood cell development. Research shows that, like AML with KMT2A rearrangements, NPM1-mutant AML depends on the interaction between two proteins, menin and KMT2A, to drive disease. Revuforj works by blocking this interaction, helping to shut down leukemia-related genes and slow disease progression.
Treatment extends survival, trial results show
AUGMENT-101 is testing the therapy in relapsed or refractory leukemias related to mutations in KMT2A or NPM1. Positive safety and efficacy results in participants with KMT2A mutations supported the approval of Revuforj for certain leukemias related to this genetic signature.
More recently, Syndax published results from 64 adults with NPM1 AML. Many had already received other therapies. Of these, nearly half responded to the therapy in a clinically meaningful way. About one-quarter achieved a complete response, though not all of them completely recovered from reduced blood cell counts.
The median survival time was four months across all participants. In those with a clinically meaningful response, the median survival was 23.3 months, or nearly two years.
In a larger group of participants, which included children with the mutation, safety results were similar to those previously reported for Revuforj. The most common serious side effect was febrile neutropenia, a condition marked by fever and low white blood cell counts, which occurred in 21.4% of participants.
Under current indications for leukemia related to KMT2A mutations, Revuforj carries a boxed warning for differentiation syndrome, a group of severe side effects with some AML therapies. In the AUGMENT-101 group with NPM1 mutations, 13.1% developed serious differentiation syndrome.
Syndax will continue to have close engagement with the FDA throughout the submission progress, as part of the Real-Time Oncology Review program. The company “is uniquely positioned to continue leading this exciting new therapeutic class with a first- and best-in-class menin inhibitor supported by compelling pivotal data across the broadest population of patients and a strong foundation already established among clinicians, payers, and other key stakeholders,” Metzger said.
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