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 the first approval of a menin inhibitor, offering a new therapeutic option for this aggressive form of leukemia.
The approval was based on data from the Phase 1/2 AUGMENT-101 trial, which evaluated 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 Revuforj treatment.
Clinical Efficacy and Safety
The efficacy evaluation was based on an analysis of 104 patients from the AUGMENT-101 trial. These results align with previously reported interim data published in the Journal of Clinical Oncology. Ghayas C. Issa, M.D., Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center, stated, "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."
The safety profile of Revuforj was assessed in 135 patients. Common adverse reactions (≥20%) included hemorrhage, nausea, increased phosphate levels, musculoskeletal pain, and infection. Serious adverse reactions occurred in 73% of patients, with infection (24%), febrile neutropenia (19%), and bacterial infection (17%) being the most frequent. The drug carries a boxed warning for differentiation syndrome, a potentially fatal condition requiring immediate corticosteroid therapy and hemodynamic monitoring.
Dosage and Availability
Syndax anticipates that Revuforj will be available in 110 mg and 160 mg tablets through a network of specialty distributors and pharmacies in November. A 25 mg tablet formulation is expected in late Q1 or early Q2 2025 for patients weighing less than 40 kg. An oral solution will be available through an expanded access program until the 25 mg tablets are commercially available.
Understanding KMT2A-Rearranged Acute Leukemia
Rearrangements of the KMT2A gene are associated with an aggressive form of acute leukemia, characterized by poor prognosis and high relapse rates. These rearrangements, particularly KMT2A translocations, result in the fusion of KMT2A proteins with menin, driving leukemogenic transcriptional activity. Revuforj inhibits this interaction, altering the transcription of genes involved in differentiation.
Syndax's Commitment
Syndax is committed to supporting patients through SyndAccess™, a program offering personalized support and financial assistance. Michael A. Metzger, CEO of Syndax, emphasized the company's dedication to advancing Revuforj's development across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML.
