FDA Grants Priority Review to Revumenib in R/R NPM1-Mutant AML

Supporting data for the sNDA came from the phase 1/2 AUGMENT-101 trial (NCT04065399) assessing revumenib among patients with relapsed/refractory NPM1-mutated AML.

The FDA has granted priority review to a supplemental new drug application (sNDA) seeking approval for revumenib (Revuforj) as a treatment for patients with relapsed/refractory acute myeloid leukemia (AML) harboring NPM1 mutations, according to a press release from the developer, Syndax Pharmaceuticals.¹

Previously, the FDA approved revumenib for patients 1 year and older with relapsed/refractory acute leukemia harboring a KMT2A translocation in November 2024.²

The FDA will review the sNDA as part of the Real-Time Oncology Review program to facilitate engagement with the developer across the submission process. Additionally, the agency set a Prescription Drug User Fee Act date of October 25, 2025, for this indication.

“We are pleased that the FDA has granted priority review to our sNDA in [relapsed/refractory NPM1-mutated] AML, a filing which builds on the initial approval of [revumenib] for [relapsed/refractory] acute leukemia with a KMT2A translocation in 2024,” Michael A. Metzger, chief executive officer at Syndax Pharmaceuticals, stated in the press release.¹

Supporting data for the sNDA came from the phase 1/2 AUGMENT-101 trial (NCT04065399) assessing revumenib among patients with relapsed/refractory NPM1-mutated AML. Investigators most recently highlighted findings from the AUGMENT-101 trial in a poster session at the 2025 European Hematology Association Congress.³

Data showed an objective response rate (ORR) of 48.1% with a complete response (CR) plus CR with partial hematologic recovery (CRh) rate of 26.0% (95% CI, 16.6%-37.2%), and a composite CR rate of 32.5% (95% CI, 22.2%-44.1%). Additionally, revumenib produced a median time to first CR or CRh of 2.8 months (range, 0.9-8.8) and a median duration of CR or CRh of 4.7 months (95% CI, 2.1-8.2).

The median overall survival (OS) was 4.8 months (95% CI, 3.4-8.4) across the entire efficacy population and 23.3 months (95% CI, 7.2-not reached [NR]) among those with a CR or CRh. Among 5 patients who proceeded to hematopoietic stem cell transplantation (HSCT), 4 were in CR or CRh, and 1 experienced a morphologic leukemia-free state. In this subgroup, 3 patients resumed treatment with revumenib as maintenance therapy.

The safety profile of revumenib in the AUGMENT-101 trial was comparable to prior reports of the agent. Grade 3 or higher treatment-emergent adverse effects (TEAEs) and treatment-related AEs (TRAEs) occurred in 91.7% and 59.5% of patients, respectively. The most common grade 3 or higher TEAEs included febrile neutropenia (33.3%), anemia (25.0%), QTc prolongation (22.6%), and decreased platelet counts (16.7%).

“These findings support continued investigation of revumenib as a treatment for [NPM1-mutated] AML in earlier lines of therapy and in combination with standard of care,” lead study author Martha L. Arellano, MD, professor in the Department of Hematology and Medical Oncology, director of the Hematology and Medical Oncology Fellowship Program, and associate director in the Division of Hematology, Department of Hematology and Medical Oncology at Emory University School of Medicine, wrote with coauthors in the poster.³

In the AUGMENT-101 trial, 84 patients with NPM1-mutated AML received revumenib at the recommended phase 2 dose at 160 mg every 12 hours orally or 95 mg/m² if their body weight was lower than 40 kg plus strong CYP3A4 inhibitors in 28-day cycles.

The trial’s primary end points were the CR plus CRh rate and safety. Secondary end points included composite CR rate, ORR, time to response, and duration of response.

Patients 30 days and older with relapsed/refractory AML harboring KMT2A rearrangements or NPM1 mutations, acute lymphoblastic leukemia, or mixed-phenotype acute leukemia were eligible for enrollment on the trial. Those with active central nervous system disease were ineligible for study entry.

References

1. Syndax announces FDA priority review of sNDA for Revuforj® (revumenib) in relapsed or refractory mNPM1 acute myeloid leukemia. News release. Syndax Pharmaceuticals. June 24, 2025. Accessed June 25, 2025. https://tinyurl.com/spy4tn6r
2. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. News release. FDA. November 15, 2024. Accessed June 25, 2025. https://tinyurl.com/yn4hesye
3. Arellano ML, Thirman MJ, DiPersio JF, et al. Revumenib for patients with relapsed or refractory (R/R) Nucleophosmin 1–mutated (NPM1m) acute myeloid leukemia (AML): updated results from the phase 2 AUGMENT-101 study. Presented at the 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract PS1467.