NEW YORK – The US Food and Drug Administration on Friday approved Syndax Pharmaceuticals' Revuforj (revumenib) as a treatment for adult and pediatric patients one year and older with relapsed or refractory acute leukemia harboring KMT2A translocations.
In a statement, Syndax highlighted that Revuforj is the "first and only menin inhibitor" for treating this biomarker-defined subset of acute leukemia patients.
The agency approved Revuforj after reviewing data from a single-arm cohort of the open-label AUGMENT-101 trial, involving approximately 100 patients at least 30 days old with relapsed or refractory acute leukemia. Patients had to have acute leukemia characterized by a KMT2A translocation to enroll in the trial; patients with an 11q23 partial tandem duplication could not participate. Patients received Revuforj until their leukemia progressed, they experienced toxicity that they couldn't tolerate, they failed to achieve a morphological leukemia-free state by the fourth cycle of treatment, or they received hematopoietic stem cell transplantation.
In the trial, 21.2 percent of patients on Revuforj achieved complete remission plus complete remission with partial hematologic recovery for a median 6.4 months. The 22 patients who achieved this status did so in a median 1.9 months.
Of the 83 patients who at baseline were receiving red blood cell or platelet transfusions, a dozen no longer needed such transfusions during the subsequent 56 days in the trial. Of the 21 patients who didn't need these transfusions at baseline, 10 remained transfusion independent during the 56-day period post-baseline.
The most common adverse reactions in the study were hemorrhage, nausea, increased phosphate levels, musculoskeletal pain, and infection, among other adverse events.
The dose of Revuforj will vary based on patients' weight and if they're simultaneously prescribed CYP3A4 inhibitors, the FDA said in a statement. The agency added that it anticipates a delay in the commercial availability of the lowest dose of the drug, which may be appropriate for patients who weigh less than 40 kg. Revuforj will be available through an expanded access program to allow access to eligible leukemia patients who weigh less than 40 kg.
Syndax said that Revuforj will be available for order in the US starting this month. "We are well prepared to launch Revuforj this month, and we are committed to rapidly advancing the development of Revuforj across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML," Syndax CEO Michael Metzger said in a statement.
Within the AUGMENT-101 trial, Syndax is also studying the drug's activity in relapsed or refractory NPM1-mutant acute myeloid leukemia. The company is expecting a topline data readout in the fourth quarter, and it hopes to submit these data within a supplemental new drug application seeking approval for Revuforj in this setting as well.