Revuforj (Revumenib), a targeted therapy for NPM1-mutated AML, is under regulatory review in the Uni

On June 24, 2025, Syndax Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted priority review to the supplemental New Drug Application (sNDA) for its first-in-class menin inhibitor Revuforj (revumenib), seeking approval for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutation. In accordance with the Prescription Drug User Fee Act (PDUFA), the FDA set the action date for the review as October 25, 2025. Previously, Revuforj was approved by the U.S. FDA in November 2024 for the treatment of certain acute leukemias with KMT2A gene rearrangement.

If approved, Revumenib will become the first menin inhibitor approved for both NPM1-mutated AML and KMT2A-rearranged acute leukemia.

NPM1 gene mutation is the most common genetic alteration in adult AML patients, accounting for approximately 30% of cases. NPM1-mutated AML is an aggressive hematologic malignancy with a high relapse rate; patients with relapsed or refractory disease have a poor prognosis and face unmet medical needs. Similar to KMT2A-rearranged acute leukemia, NPM1-mutated AML is highly dependent on the menin-KMT2A interaction, and disruption of this interaction has been shown to result in the downregulation of key leukemogenic genes. NPM1-mutated AML is routinely diagnosed using existing screening technologies, and there are currently no approved therapies that selectively target the underlying disease mechanisms driving NPM1-mutated AML.

Revumenib, a menin inhibitor, is an oral targeted therapy that blocks the interaction between menin and KMT2A fusion proteins, thereby inhibiting cancer cell proliferation, promoting differentiation, and slowing or halting tumor growth. Menin is a protein endogenously expressed in human cells.

As the first approved oral menin inhibitor, Revumenib offers a novel precision treatment option for patients with relapsed or refractory NPM1-mutated AML—an underserved population that previously relied on chemotherapy or other targeted agents (e.g., FLT3 inhibitors) with low remission rates and poor prognosis after relapse. Through its unique mechanism of action, Revumenib achieves clinically meaningful remission rates and durable responses, and its oral formulation improves treatment convenience and patient adherence.

The phase 2 AUGMENT-101 trial (NCT04065399) evaluated the efficacy and safety of Revumenib in patients with relapsed/refractory AML harboring NPM1 mutation. The trial results were presented at the 2025 European Hematology Association (EHA) Congress.

Patients received Revumenib at a dose of 160 mg every 12 hours when co-administered with a strong CYP3A4 inhibitor, or 270 mg every 12 hours in the absence of a strong CYP3A4 inhibitor, in 28-day treatment cycles. Treatment continued until the occurrence of unacceptable toxicity, disease progression, or lack of response after four or more cycles. The safety population included all patients who received at least one dose of Revumenib, and the efficacy-evaluable population comprised patients with centrally confirmed NPM1 mutation. A total of 84 patients were enrolled, with 74 meeting the criteria for efficacy analysis.

The primary endpoints were the rate of complete remission plus complete remission with partial hematologic recovery (CR+CRh), safety, and tolerability. Secondary endpoints included the objective response rate (ORR) and duration of response (DOR). Measurable residual disease (MRD) testing was performed at the investigator’s discretion using polymerase chain reaction (PCR) or flow cytometry at local laboratories.

Results demonstrated that Revumenib induced clinically meaningful and durable responses in heavily pretreated patients with NPM1-mutated AML. The CR+CRh rate was 26.0% (95% CI, 16.6%-37.2%), and the ORR was 48.1% (95% CI, 36.5%-59.7%).

The median duration of CR+CRh was 4.7 months (95% CI, 2.1-8.2), with a median time to first CR+CRh of 2.76 months (range: 0.9-8.8). Among 19 patients who achieved CR+CRh with available MRD status, 12 (63.2%) achieved MRD negativity (6 via PCR, 6 via flow cytometry); the median time to first MRD negativity was 2.78 months (range: 1.8-4.7).

The safety profile of Revumenib was consistent with previous reports. In the safety population, treatment-related adverse events (TRAEs) occurred in 66 patients (78.6%), with 50 patients (59.5%) experiencing grade 3 or higher TRAEs. The most common grade 3 or higher TRAEs included prolonged QTc interval (18 patients [21.4%]), anemia (12 patients [14.3%]), febrile neutropenia (11 patients [13.1%]), differentiation syndrome (11 patients [13.1%]; 9 grade 3 [10.7%], 2 grade 4 [2.4%]), and thrombocytopenia (9 patients [10.7%]). TRAEs led to treatment discontinuation in 4 patients (4.8%) and death in 1 patient (1.2%).

The study results for this patient population have also been published in the journal Blood.