The U.S. Food and Drug Administration (FDA) approved enasidenib, an isocitrate dehydrogenase-2 (IDH2) inhibitor, for adults with relapsed/refractory IDH2-mutated acute myeloid leukemia (AML). The drug is approved for use with the RealTime IDH2 Assay, a companion diagnostic that can detect specific mutations in the IDH2 gene in this patient population.
The approval was based on the results of the single-arm, phase I/II AG221-C-001 study, which included 199 patients (median age = 68 years; range = 19-100 years) with relapsed/refractory IDH2-mutated AML that was detected by the RealTime IDH2 Assay. Patients had received a median of two prior therapies (range = 1-6 therapies).
After a minimum of six months of treatment, 19.3 percent of patients (95% CI 13.8-25.9) who received enasidenib experienced a CR for a median of 8.2 months, and 4 percent of patients experienced a CR with partial hematologic recovery for a median of 9.6 months. Of the 157 patients who required blood or platelet transfusions at baseline, 34 percent no longer required transfusions after receiving enasidenib.
The most common AEs associated with enasidenib included nausea, vomiting, diarrhea, increased bilirubin levels, and decreased appetite.
The drug carries a boxed warning that differentiation syndrome can occur and can be fatal if left untreated. Differentiation syndrome is associated with fever; dyspnea; acute respiratory distress; radiographic pulmonary infiltrates; pleural or pericardial effusions; rapid weight gain; peripheral edema; or hepatic, renal, or multi-organ dysfunction.
The FDA previously granted enasidenib priority review and orphan-drug designation.
Source: U.S. Food and Drug Administration news release, August 1, 2017.