Syndax Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review to its New Drug Application (NDA) for revumenib, a first-in-class menin inhibitor, for the treatment of adult and pediatric patients with relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia. The FDA's decision is anticipated by September 26, 2024.
The NDA submission is based on data from the pivotal AUGMENT-101 trial, a Phase 2 study evaluating revumenib in patients with R/R KMT2Ar acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The trial met its primary endpoint, demonstrating a complete remission (CR) or complete remission with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8], one-sided p-value = 0.0036) among the 57 efficacy-evaluable patients in the pooled KMT2Ar acute leukemia population. Notably, 70% of patients who achieved CR/CRh and were assessed for minimal residual disease (MRD) were MRD negative.
AUGMENT-101 Trial Details
The AUGMENT-101 trial enrolled adult and pediatric patients with R/R KMT2Ar acute leukemia. In the efficacy-evaluable population, 63% (36/57) achieved an overall response. Of these responders, 39% (14/36) underwent hematopoietic stem cell transplant (HSCT), with 50% (7/14) restarting revumenib as post-transplant maintenance at the time of the data cutoff.
Revumenib: A Menin-KMT2A Inhibitor
Revumenib is a selective, small molecule inhibitor of the menin-KMT2A binding interaction. It is under development for the treatment of KMT2A-rearranged acute leukemias, including ALL and AML, as well as NPM1-mutant AML. The FDA has granted revumenib Orphan Drug Designation for AML and Fast Track designation for R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib also holds Breakthrough Therapy Designation for R/R acute leukemia with a KMT2A rearrangement.
Real-Time Oncology Review Program
The FDA is reviewing the NDA under the Real-Time Oncology Review (RTOR) program, designed to expedite the availability of safe and effective treatments for cancer patients. RTOR facilitates close engagement between the sponsor and the FDA throughout the submission process, allowing for a more efficient review.
Syndax's Perspective
"The receipt of Priority Review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," said Michael A. Metzger, Chief Executive Officer of Syndax Pharmaceuticals. "With two regulatory filings now under FDA Priority Review, our team is focused on commercial preparations to enable Syndax's continued success as we enter this next stage of growth."
