FDA Approves Revumenib for Relapsed/Refractory NPM1-Mutant Acute Myeloid Leukemia

The FDA has approved revumenib (Revuforj) for the treatment of adult and pediatric patients at least 1 year of age with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation who do not have satisfactory alternative treatment options.1

This approval follows priority review of the supplemental new drug application, submitted on June 25, 2025, and is supported by findings from the phase 1/2 AUGMENT-101 trial (NCT04065399).1,2 In AUGMENT-101, the complete response (CR)/CR with partial hematological recovery (CRh) rate with revumenib (n = 65) was 23.1% (95% CI, 13.5%-35.2%), and the median duration of CR/CRh was 4.5 months (95% CI, 1.2-8.1).1,3 The CR rate was 18.5% (95% CI, 9.9%-30%), and the median duration of CR was 3.7 months (95% CI, 1.0-8.1).3 Additionally, the CRh rate was 4.6% (95% CI, 1.0%-12.9%), and the observed duration of CRh was 1.8 months (95% CI, 2.0-4.5).

Among patients dependent on red blood cell (RBC) and/or platelet transfusions at baseline (n = 46), 17% became independent of RBC and platelet transfusions during any 56-day post-baseline period.1,3 Among patients who achieved a CR or CRh (n = 15), the median time to response (TTR) was 2.8 months (range, 1.8-9.6).3

Notably, the revumenib prescribing information includes warnings and precautions for differentiation syndrome, QTc interval prolongation and Torsades de Pointes, and embryo-fetal toxicity.1,3

Additionally, the recommended dose of revumenib varies by patient weight and concomitant use of strong CYP3A4 inhibitors. Hematologists are advised to consult the revumenib prescribing information for specific dosage guidance.

AUGMENT-101 Background and Trial Design

Revumenib previously received FDA approval in November 2024 for adult and pediatric patients aged 1 year and older with relapsed/refractory acute leukemia harboring a KMT2A translocation, based on earlier AUGMENT-101 results.4 The study enrolled patients at least 30 days old with relapsed/refractory KMT2A-rearranged or NPM1-mutant AML, acute lymphoblastic leukemia, or mixed-phenotype acute leukemia.5

Eligible patients received revumenib at 160 mg orally every 12 hours, or at 95 mg/m2 if body weight was under 40 kg, administered with a strong CYP3A4 inhibitor in 28-day cycles. Patients achieving a partial response or better were permitted to proceed to hematopoietic stem cell transplant (HSCT), with the option to resume revumenib if a composite complete response (CRc) was achieved post-transplant.

The primary end points of AUGMENT-101 included CR or CR/CRh, along with safety. Secondary end points included CRc, objective response rate (ORR), TTR, and duration of response.

Efficacy Results in NPM1-Mutant AML

Additional results from the NPM1-mutant AML cohort (n = 77) were presented at the 2025 EHA Congress. The median patient age was 63 years (range, 11-84), with most patients being female (58.4%) and White (55.8%). Nearly half of patients had relapsed/refractory disease (49.4%), whereas 28.6% of patients had early untreated relapse. Common co-occurring mutations included FLT3-ITD (29.9%), IDH1 (14.3%), and IDH2 (13.0%). Patients had received a median of 2 prior lines of therapy, including venetoclax (Venclexta; 74.0%), FLT3 inhibitors (40.3%), and HSCT (23.4%).

The previously reported CR/CRh rate was 26.0% (95% CI, 16.6%-37.2%). Responses were observed rapidly, with a median time to first CR/CRh of 2.8 months (range, 0.9-8.8). The median duration of CR/CRh was 4.7 months (95% CI, 2.1-8.2).

The CRc rate reached 32.5% (95% CI, 22.2%-44.1%), and the ORR was 48.1%. Best 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%), and partial response (2.6%). The median time to ORR was 1.8 months (range, 0.8-4.6).

The median overall survival (OS) across the cohort was 4.8 months (95% CI, 3.4-8.4). Notably, patients achieving CR/CRh (n = 20) had a median OS of 23.3 months (95% CI, 7.2-not reached).

References

1. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. FDA. October 24, 2025. Accessed October 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation
2. 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 October 24, 2025. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-priority-review-snda-revuforjr-revumenib
3. Revuforj. Prescribing information. Syndax. Updated October 2025. Accessed October 24, 2025. https://cms.syndax.com/wp-content/uploads/Revuforj-full-prescribing-info.pdf
4. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. FDA. November 15, 2024. Accessed October 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation
5. Arellano ML, Thirman M, DiPersio J, et al. 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 EHA Congress. June 12-15, 2025; Milan, Italy. Abstract PS1467.