FDA Approves Revuforj (revumenib) for Relapsed/Refractory Acute Leukemia with KMT2A Translocation
Key Insights
The FDA has approved Revuforj (revumenib) as the first menin (search) inhibitor for relapsed or refractory acute leukemia (search) with a KMT2A translocation (search) in patients aged one year and older.
Efficacy was demonstrated in the AUGMENT-101 trial, with a complete remission rate of 21% in patients treated with Revuforj, and 23% proceeding to stem cell transplantation.
Revuforj's approval marks a significant advancement for patients with KMT2A-rearranged acute leukemia (search), who typically face poor prognoses and limited treatment options.
The U.S. Food and Drug Administration (FDA) has granted approval to Revuforj (revumenib), a first-in-class menin (search) inhibitor, for the treatment of relapsed or refractory acute leukemia (search) with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older. This approval marks a significant advancement in the treatment of this aggressive form of leukemia, which is associated with poor prognosis and high relapse rates. Syndax Pharmaceuticals made the announcement on November 15, 2024.
Clinical Efficacy and Safety
The efficacy of Revuforj was evaluated based on data from the Phase 1/2 AUGMENT-101 trial, which included 104 patients with relapsed or refractory acute leukemia (search) with a KMT2A translocation (search). The results showed 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 patients) underwent hematopoietic stem cell transplantation (HSCT) following treatment with Revuforj.
The safety evaluation was based on 135 patients with relapsed or refractory acute leukemia (search) with a KMT2A translocation (search). Common adverse reactions (≥20%) included hemorrhage (53%), nausea (51%), increased phosphate (50%), musculoskeletal pain (42%), and infection (41%). Serious adverse reactions occurred in 73% of patients, with the most frequent being infection (24%), febrile neutropenia (19%), and bacterial infection (17%).
Expert Commentary
Ghayas C. Issa, M.D., Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center, commented on the approval, stating, "The FDA approval of the first menin (search) inhibitor is a major breakthrough for patients with R/R acute leukemia (search) with a KMT2A translocation (search), a genetic alteration associated with a very poor prognosis. 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."
Disease Context and Unmet Need
Rearrangements of the KMT2A gene (KMT2Ar) are present in an aggressive form of acute leukemia (search), with over 95% of patients having a KMT2A translocation (search). More than half of these patients relapse after conventional frontline therapies, with a median overall survival of less than one year. In third-line treatment or beyond, only 5% of patients achieve complete remission, and the median overall survival is less than three months, highlighting the urgent need for new therapeutic options.
Dosing and Availability
Syndax expects that the 110 and 160 mg tablets of Revuforj will be available for order in the United States through a network of specialty distributors and specialty pharmacies in November. The 25 mg tablets, intended for patients weighing less than 40 kg, are expected to be available in late first quarter or early second quarter of 2025. An oral solution of revumenib will be available through an expanded access program for these patients until the 25mg tablets are commercially available.
Differentiation Syndrome Warning
The prescribing information for Revuforj includes a boxed warning for differentiation syndrome, a potentially fatal condition. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. The warning advises immediate initiation of corticosteroid therapy and hemodynamic monitoring if differentiation syndrome is suspected.
About Syndax Pharmaceuticals
Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company focused on developing cancer therapies. Their pipeline includes Revuforj (revumenib) and Niktimvo (axatilimab-csfr).