August 1, 2017
On August 1, 2017, the U.S. Food and Drug Administration granted regular approval to enasidenib (IDHIFA®, Celgene Corp.) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.
This is the first FDA approval for relapsed or refractory AML specifically with an IDH2 mutation. The FDA concurrently approved a companion diagnostic, the RealTime IDH2 Assay, used to detect the IDH2 mutation.
The enasidenib approval was based on Study AG221-C-001 (NCT01915498), an open-label, single-arm, multicenter, clinical trial of enasidenib that included 199 adults with relapsed or refractory AML who had an IDH2 mutation as detected by the above assay. Patients were treated with enasidenib 100 mg orally daily. Complete response (CR) and complete response with partial hematologic recovery (CRh) rates, CR/CRh duration, and conversion from transfusion dependence to transfusion independence were the basis of approval.
After a median follow-up time of 6.6 months, 23% of patients experienced CR or CRh lasting a median of 8.2 months, with 19% of patients having a CR lasting a median 8.2 months, and 4% with a CRh lasting a median 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-best response of CR/CRh was 3.7 months (range, 0.6 to 11.2 months). Of the 157 patients who required transfusions at the initiation of the trial, 34% no longer required transfusions during at least one 56-day time period on enasidenib. Of the 42 patients who did not require transfusions at the start of the trial, 76% maintained transfusion independence.
The most common adverse reactions occurring in greater than 20% of patients were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite. Differentiation syndrome occurred in 14% of patients. As differentiation syndrome may be fatal without prompt management, the prescribing information includes a boxed warning and instructions on the risk and need for early intervention.
The recommended dose of enasidenib is 100 mg orally once daily until disease progression or unacceptable toxicity.
Full prescribing information is available at:
FDA previously granted Orphan Drug and Fast Track designations to enasidenib for the treatment of AML, as well as priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).