On Nov. 15, 2024, Syndax Pharmaceuticals announced that the US Food and Drug Administration (FDA) approved Revuforj^® (revumenib) ahead of the proposed Dec. 26, 2024, decision date. This is the first menin inhibitor 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 approval offers a new class of drugs for an aggressive form of cancer. Revuforj carries a boxed warning for differentiation syndrome, which can be fatal. Other warnings include QTc interval prolongation and embryo-fetal toxicity. The recommended dose is based on a patient’s weight and if they are concomitantly taking a strong CYP3A4 inhibitor. It is administered orally twice a day, either fasting or with a low-fat meal. The wholesale acquisition cost (WAC) will be $474,000 annually. The 110mg and 160mg tablets of Revuforj will be available later this month, while the 25mg tablets are expected to launch in early 2025. For full prescribing information, click here.

At a Glance

• Brand Drug: Revuforj^® (revumenib)
• Manufacturer: Syndax Pharmaceuticals
• Date Approved: Nov. 15, 2024
• Indication:  Relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older
• Dosage Forms Available: 25mg, 110mg, 160mg tablets
• Launch Date: The 110mg and 160mg tablets of Revuforj will be available in November.
• Estimated Annual Cost: $474,000 per year
• The American Cancer Society (ACS) estimates that roughly 60,000 patients are diagnosed with any form of leukemia in the US annually and that approximately 20,800 will have acute myeloid leukemia (AML). AML is a cancer of the bone marrow that may be refractory. Leukemia cells remain in the bone marrow even after intensive treatment, or relapsed, remission is reached but then a return of leukemia cells. About 6,550 new cases of acute lymphocytic leukemia (ALL) are diagnosed each year in the US. ALL is a cancer of a type of white blood cells called lymphocytes.
• Around one-tenth of all leukemias are believed to have KMT2A rearrangements, which have a five-year survival rate of only about 25%. This mutation is most common in infants and children.
• Approval is based on the Augment-101 trial, an open-label phase I/II clinical trial of revumenib as monotherapy for 104 adults and children who have R/R KMT2A-rearranged AML or ALL.  Complete remission or complete remission with partial hematologic recovery was achieved in 21.2% of patients. Patients began to react to treatment with revumenib after an average of 1.9 months and responses lasted an average of 6.4 months. Twenty-four individuals, 23% of participants in the study, progressed to hematopoietic stem cell transplant after treatment with Revuforj.
• The most common side effects were hemorrhage, nausea, severe reaction to treatment (differentiation syndrome), and heart arrhythmia (QTc prolongation). Dose reduction or discontinuation due to adverse effects occurred in about 10% of patients.
• No other drugs are currently FDA-approved specifically to treat leukemias that have KMT2A rearrangements or nucleophosmin (NPM1) mutations. In general, the standard treatment for most leukemias is chemotherapy (chemo). Many patients receive stem cell transplants following chemo or other drug therapy.
• Kura Oncology’s ziftomenib and Sumitomo Pharma’s enzomenib are KMT2A inhibitors in Phase II development for treating patients with R/R AML.
• Revuforj is also expected to submit for approval in R/R mutant NPM1 AML in the first half of 2025 based on positive topline clinical trial results.