FDA Grants Priority Review to Revumenib for Relapsed/Refractory NPM1-Mutant AML

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The FDA has granted priority review to the supplemental new drug application (sNDA) for revumenib (Revuforj) for the treatment of patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML).1

The sNDA, which is supported by data from the phase 1/2 AUGMENT-101 trial (NCT04065399), is being reviewed under the FDA’s Real-Time Oncology Review program, allowing for a more efficient review and closer alignment between the sponsor and the FDA throughout the submission process.

The agency has set a Prescription Drug User Fee Act target action date of October 25, 2025.

“We are pleased that the FDA has granted priority review to our sNDA in [relapsed/refractory] NPM1[-mutant] 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 of Syndax, said in a news release. “Syndax 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.”

In November 2024, the FDA approved revumenib for the treatment of adult and pediatric patients 1 year and older with relapsed/refractory acute leukemia with KMT2A translocation based on findings from AUGMENT-101.2

The AUGMENT-101 trial enrolled patients at least 30 days old with relapsed/refractory KMT2A-rearranged or NPM1-mutant AML, acute lymphoblastic leukemia, or mixed-phenotype acute leukemia.3 Eligible patients received 160 mg of revumenib orally every 12 hours, or 95 mg/m2 if body weight fell under 40 kg, plus a strong CYP3A4 inhibitor in 28-day cycles. If a partial response or better was achieved, patients had the option of undergoing hematopoietic stem cell transplant (HSCT) and receiving additional revumenib thereafter if a composite complete response (CRc) was subsequently achieved.

The primary end points were CR/CR with partial hematologic recovery (CRh), as well as safety. Secondary end points included CRc, objective response rate (ORR), time to response, and duration of response.

Updated findings from the cohort of efficacy-evaluable patients with NPM1-mutant AML (n = 77) were presented at the 2025 EHA Congress. Patients had a median age of 63 years (range, 11-84), and most were female (58.4%), White (55.8%), and had either relapsed/refractory (49.4%) or early untreated relapse (28.6%) at baseline. The most common co-occurring mutations were FLT3-ITD (29.9%), IDH1 (14.3%), and IDH2 (13.0%). The median number of prior lines of therapy was 2 (range, 1-7), and prior therapies included venetoclax (Venclexta; 74.0%), a FLT3 inhibitor (40.3%), and HSCT (23.4%).

The results indicated that the CR/CRh rate within the efficacy population was 26.0% (95% CI, 16.6%-37.2%). The median time to first CR/CRh was 2.8 months (range, 0.9-8.8), and the median duration of CR/CRh was 4.7 months (95% CI, 2.1-8.2).

The CRc rate was 32.5% (95% CI, 22.2%-44.1%), and the ORR was 48.1%. Best overall responses included CR (20.8%), CRh (5.2%), CR with incomplete hematologic recovery (2.6%), CR with incomplete platelet recovery (3.9%), morphologic leukemia-free state (13.0%), partial response (2.6%), progressive disease (6.5%), no response (28.6%), and other (16.9%). The median time to first ORR was 1.8 months (range, 0.8-4.6).

The median overall survival (OS) was 4.8 months (95% CI, 3.4-8.4). The median OS in CR/CRh responders (n = 20) was 23.3 months (95% CI, 7.2-not reached).

The safety profile of the agent remained consistent with that of prior reports, with fewer than 5% of patients discontinuing treatment because of a treatment-related adverse effect.

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://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-priority-review-snda-revuforjr-revumenib
2. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. FDA. November 15, 2024. Accessed June 25, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation
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: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract PS1467.