Syndax Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved Revuforj® (revumenib) for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older. This marks Revuforj as the first and only menin inhibitor to receive FDA approval for this indication.
The approval was based on data from the Phase 1/2 AUGMENT-101 trial, which evaluated the efficacy of Revuforj in patients with R/R acute leukemia with a KMT2A translocation. The study demonstrated a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 21% (22/104 patients; 95% CI: 13.8%, 30.3%). The median duration of CR+CRh was 6.4 months (95% CI: 2.7, not estimable), and the median time to CR or CRh was 1.9 months (range: 0.9, 5.6 months). Notably, 23% (24/104) of patients underwent hematopoietic stem cell transplantation (HSCT) following treatment with Revuforj.
Clinical Efficacy and Safety
The efficacy evaluation was based on an FDA analysis of 104 patients. The safety profile of Revuforj was assessed in 135 patients with R/R acute leukemia with a KMT2A translocation. Common adverse reactions (≥20%) included hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, prolonged electrocardiogram QT, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, and fatigue.
Addressing an Unmet Need
Rearrangements of the KMT2A gene (KMT2Ar) are associated with an aggressive form of acute leukemia, characterized by poor prognosis and high relapse rates. It is estimated that over 95% of patients with KMT2Ar acute leukemia have a KMT2A translocation. More than half of these patients relapse after conventional frontline therapies, with a median overall survival (OS) of less than one year. In later lines of treatment, only 5% achieve complete remission, and the median OS is less than three months.
Revuforj's Mechanism of Action
In KMT2Ar acute leukemias, the binding of KMT2A fusion proteins with menin drives the activation of a leukemogenic transcriptional pathway. Revumenib inhibits the menin-KMT2A interaction, altering the transcription of multiple genes, including differentiation markers.
Syndax's Commitment
Syndax expects Revuforj to be available for order in the United States this month through a network of specialty distributors and pharmacies. The company has also established SyndAccess™ to provide personalized support and financial assistance to eligible patients.
"The FDA approval of the first menin inhibitor is a major breakthrough for patients with R/R acute leukemia with a KMT2A translocation, a genetic alteration associated with a very poor prognosis," said Ghayas C. Issa, M.D., Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center. "The significant clinical benefit and robust efficacy seen with Revuforj represents a substantial improvement over what has been historically observed in these patients with previously available therapies and has the potential to be an important new treatment option for patients."
