FDA Approves Revumenib in Mutant NPM1 AML

The FDA has approved the supplemental new drug application (sNDA) for revumenib (Revuforj) in the treatment of relapsed or refractory (R/R) mutant nucleophosmin 1 (mNPM1) acute myeloid leukemia (AML) after receiving priority review.^1,2

The sNDA decision is supported by positive data from the phase 2 portion of the AUGMENT-101 trial (NCT04065399), which were presented at the European Hematology Association (EHA) 2025 Congress. Here, the primary end point of complete remission (CR) and complete remission with partial hematologic recovery (CRh) was achieved in 26% of patients in the efficacy population (n = 20/77; 95% CI, 17%-37%).^3,4 Furthermore, the median duration of CR/CRh was 4.7 months (95% CI, 2.1-8.2), and the median time to first CR/CRh was 2.8 months (range, 0.9-8.8).

The agent also demonstrated a safety profile consistent with prior reports. Among patients in the safety population, 98.8% (n = 83/84) experienced treatment-emergent adverse events (TEAEs), with the most frequently occurring any-grade TEAEs being QTc prolongation (42.9%), vomiting (36.9%), febrile neutropenia (34.5%), hypokalemia (32.1%), and nausea (28.6%). Differentiation syndrome of any grade had occurred as a TEAE in 19% (n = 16) of the safety population, which was managed with corticosteroids. Differentiation syndrome led to discontinuation in 1 patient. Furthermore, less than 5% of participants discontinued treatment due to treatment-related adverse events (TRAEs), with 1 death (1.2%) reported due to a TRAE (cardiac arrest).

In 2024, revumenib was approved by the FDA for use in R/R acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients, also supported by AUGMENT-101 data. With the recent approval in mNPM1 AML, the most common mutation in AML,¹ revumenib’s function expands to another indication with critical unmet medical need, including high relapse rates and poor prognosis, and for which there were no previously approved therapies targeting the variant.

The phase 1/2 AUGMENT-101 trial is an open-label study evaluating revumenib, an oral menin inhibitor, in adult and pediatric patients with R/R mNPM1 or KMT2A acute leukemias.⁵ The population harboring an NPM1 mutation (n = 84) was older and heavily pretreated, with nearly half (48.8%) of the population over aged 65 years and 35% having received 3 or more prior lines of therapy.³

The study’s primary end points are rate of CR + CRh, safety, and tolerability; secondary end points include composite complete remission, overall response rate, time to response, duration of response, event-free survival, and overall survival.

The study is actively recruiting, with an estimated enrollment of 413 and an estimated completion slated for December 2027.

REFERENCES:

1. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. News release. FDA. October 24, 2025. https://tinyurl.com/y5jd4ss5

2. Syndax Announces FDA Priority Review of sNDA for Revuforj® (revumenib) in Relapsed or Refractory mNPM1 Acute Myeloid Leukemia. News release. Syndax Pharmaceuticals. Published June 24, 2025. Accessed September 29, 2025. https://tinyurl.com/4nr6t6b3

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. Poster presented at: European Hematology Association Annual Congress Meeting; June 12–15, 2025; Milan, Italy.

4. Arellano ML, Thirman MJ, DiPersio JF, et al. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025;146(9):1065–1077. doi:doi.org/10.1182/blood.2025028357

5. A Study of Revumenib in R/​R Leukemias Including Those With an MLL/​KMT2A Gene Rearrangement or NPM1 Mutation (AUGMENT-101). ClinicalTrials.gov. Updated September 4, 2025. Accessed September 29, 2025.https://clinicaltrials.gov/study/NCT04065399