Syndax Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved Revuforj (revumenib) for the treatment of relapsed or refractory (R/R) 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 such approval.
The FDA granted Breakthrough Therapy and Fast Track designations, as well as Priority Review for Revuforj. The New Drug Application (NDA) received approval through the FDA's Real Time Oncology Review (RTOR) program.
Clinical Efficacy
The efficacy evaluation of Revuforj was based on an FDA analysis of 104 patients with R/R acute leukemia with a KMT2A translocation who were treated with Revuforj in the Phase 1/2 AUGMENT-101 trial. The rate of complete remission (CR) plus CR with partial hematological recovery (CRh) was 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). Twenty-three percent (24/104 patients) of patients underwent hematopoietic stem cell transplantation (HSCT) following treatment with Revuforj.
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 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."
Safety Profile
The safety evaluation of Revuforj was based on an FDA analysis of 135 patients with R/R acute leukemia with a KMT2A translocation who were treated with Revuforj. The most common adverse reactions (≥20%) including laboratory abnormalities were hemorrhage, nausea, phosphate increased, musculoskeletal pain, infection, aspartate aminotransferase increased, febrile neutropenia, alanine aminotransferase increased, parathyroid hormone intact increased, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, phosphate decreased, triglycerides increased, potassium decreased, decreased appetite, constipation, edema, viral infection, fatigue, and alkaline phosphatase increased. Adverse reactions leading to dose reduction or permanent discontinuation were low at 10% and 12% of patients, respectively.
Disease Context
Rearrangements of the KMT2A gene (KMT2Ar) give rise to an aggressive form of acute leukemia that is associated with a very poor prognosis and high relapse rates. It is estimated that more than 95% of patients with KMT2Ar acute leukemia have a KMT2A translocation. More than half of patients with KMT2Ar acute leukemia will relapse after receiving conventional frontline therapies, with a median overall survival (OS) of less than one year. With third line treatment or beyond, only 5% of patients achieve complete remission, and the median OS is less than three months.
Availability and Support
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. Syndax expects that the 25 mg tablets, which may be used to treat patients who weigh less than 40 kg, will be commercially available in late first quarter or early second quarter of 2025. Prior to commercial availability of the 25 mg tablets, an oral solution of revumenib will be available through an expanded access program to allow for dosing of patients who weigh less than 40 kg.
Syndax is committed to supporting patients and removing barriers to access. As part of that commitment, Syndax has established SyndAccess™, a program that offers personalized support and resources to U.S. patients who are prescribed Revuforj, including financial assistance for eligible patients.
About Revuforj (revumenib)
Revuforj (revumenib) is an oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.
Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1).
