Syndax Pharmaceuticals' Revuforj (revumenib) has received FDA approval, marking it as the first and only menin inhibitor for the treatment of relapsed or refractory acute leukemia in adult and pediatric patients (one year and older) with a lysine methyltransferase 2A gene (KMT2A) translocation. This approval addresses a critical unmet need in patients with this rare and aggressive form of leukemia.
The approval was primarily based on data from the AUGMENT-101 clinical trial. The study demonstrated that 21% of patients treated with Revuforj achieved complete remission with partial hematological recovery. This outcome is particularly significant given that only about 5% of patients with this mutation achieve complete remission with current third-line treatments, which have a median overall survival rate of less than three months.
Mechanism of Action and Prevalence
Revuforj functions by inhibiting the menin protein, which is crucial for KMT2A-rearranged leukemia cells to proliferate. KMT2A translocations are found in approximately 10% of all leukemias, with an estimated 95% of KMT2A acute leukemia patients having this specific genetic abnormality. Michael Metzger, CEO and director of Syndax, stated that this approval marks a major milestone in the leukemia community, emphasizing the company's commitment to launching Revuforj in the United States.
Adverse Reactions and Safety Profile
The safety evaluation of Revuforj was based on an analysis of 135 patients. Serious adverse reactions were observed in 73% of patients, with 3% of patients experiencing fatal outcomes. Differentiation syndrome, a known complication of certain blood cancer drugs, was responsible for two of the deaths. Other serious adverse reactions included infection (24%), febrile neutropenia (19%), and bacterial infection (17%). Common adverse reactions included hemorrhage (53%), nausea (51%), and increased phosphate (50%), leading to dose interruptions in 42% of patients. Patients should be monitored closely for signs and symptoms of differentiation syndrome and other potential complications.
Dosage, Availability, and Support
Revuforj will be available in 110 mg and 160 mg tablets, administered twice daily depending on the patient's weight. A 25 mg tablet option for patients weighing less than 40 kg is expected in late Q1 or early Q2 2025; until then, an oral solution will be available through an expanded access program. The wholesale acquisition price is $39,500 for a 30-day supply of either the 110 mg or 160 mg tablets. Syndax will offer financial assistance through SyndAccess, a new support and resource program for patients.
The FDA had previously granted Revuforj Breakthrough Therapy, Fast Track, and Priority Review designations. The New Drug Application was reviewed through the FDA's Real Time Oncology Review program, expediting its approval.
