On August 1, 2017, the U.S. Food and Drug Administration (FDA) officially approved IDHIFA (enasidenib) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with isocitrate dehydrogenase-2 (IDH2) mutations.
This is the first time the FDA has approved a drug for the treatment of relapsed or refractory AML with IDH2 mutations. The FDA also approved a complementary diagnostic method, real-time IDH2 testing, for detecting IDH2 mutations.
The approval of enasidenib is based on Study AG221-C-001 (NCT01915498). This was an open-label, single-arm, multicenter clinical trial of enasidenib that included 199 adults with relapsed or refractory AML due to IDH2 gene mutations. Patients received 100 mg of enasidenib orally daily. Complete response (CR) and complete response to partial hematologic recovery (CRh) rates, CR/CRh duration, and the transition from transfusion dependence to transfusion independence were the basis for approval.
After a median follow-up of 6.6 months, 23% of patients had a median CR or CRh duration of 8.2 months, 19% had a median CR duration of 8.2 months, and 4% had a median CRh duration of 9.6 months. The median time to first response was 1.9 months (range 0.5 to 7.5 months), and the median time to optimal CR/CRh response was 3.7 months (range 0.6 to 11.2 months). Of the 157 patients who required transfusions at the start of the trial, 34% no longer required transfusions within at least one 56-day cycle of enasidenib. Of the 42 patients who did not require transfusions at the start of the trial, 76% remained transfusion-independent.
The most common adverse reactions occurring in more than 20% of patients are nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite; differentiation syndrome occurs in 14% of patients. Because differentiation syndrome can be fatal if not treated promptly, the prescribing information includes boxed warnings and information about the risks and the need for early intervention.
The recommended dose is 100 mg enasidenib orally daily until disease progression or unacceptable toxicity occurs in the patient.
