FDA Approves First and Only Drug for Rare Leukemia

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Syndax Pharmaceuticals recently announced the FDA approval of Revuforj (revumenib) for the treatment of relapsed or refractory acute leukemia in adult and pediatric patients one year and older. It is indicated for patients with a lysine methyltransferase 2A gene (KMT2A) translocation, according to a news release.

“Today marks another major milestone in the leukemia community,” Michael Metzger, CEO and director of Syndax said during the investor call. “With the FDA approval in hand, we look forward to launching Revuforj in the United States this month.”

Revuforj is the first and only menin inhibitor approved by the FDA. It works by preventing rearrangements in KMT2A gene, which can lead to the development of leukemia cells. An estimated 95% ofKMT2Ar acute leukemia patients have KMT2A translocation. This abnormality is seen in about 10% of all leukemias.

Only about 5% of patients with this mutation achieve complete remission with current third-line treatment with a median overall survival rate of less than three months, according to the news release. More than half of patients will relapse after first-line treatment.

The approval of Revuforj is based on positive data from the AUGMENT-101 clinical trial in which 21% of patients reached complete remission with partial hematological recovery, meaning that although no was cancer detected, blood cell counts have not fully recovered. This took about six months.

Safety evaluation of Revuforj was based on an analysis of 135 patients. Serious adverse reactions were seen in 73% of patients and 3% of patients died. Two patients died from differentiation syndrome, one hemorrhaged and another “died suddenly,” the news release reports. Differentiation syndrome is a side effect of certain blood cancer drugs that can present as trouble breathing, fever and weight gain. It is fatal within the first few weeks of treatment.

The most common serious adverse reactions were infection (24%), febrile neutropenia (19%) and bacterial infection (17%). The most common adverse reactions were hemorrhage (53%), nausea (51%) and increased phosphate (50%). As a result, dose interruptions occurred in 42% of patients.

Revuforj will be available as 110 mg and 160 mg tablets to be taken twice daily, depending on weight. It’s expected to be available via specialty pharmacies later this month. There will also be a 25 mg tablet option for patients who weigh less than 40 kg, expected late in the first quarter or early second quarter of 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 the 110 or 160 mg tablets, according to the investor call.  

Syndax will eventually offer financial assistance via SyndAccess, a newly established support and resource program for patients.

The FDA previously granted Revuforj Breakthrough Therapy, Fast Track and Priority Review designations. A New Drug Application was granted through FDA's Real Time Oncology Review program.