August 01, 2017
2 min read

FDA approves Idhifa for IDH2-mutated acute myeloid leukemia

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The FDA approved enasidenib for the treatment of adults with relapsed or refractory acute myeloid leukemia with an IDH2 mutation as detected by an FDA-approved test, according to the drug’s manufacturer.

Enasidenib (Idhifa; Celgene, Agios) — an oral targeted inhibitor of the IDH2 enzyme — is approved for use with the companion diagnostic RealTime IDH2 Assay (Abbott Laboratories), used to detect specific mutations in the IDH2 gene in patients with AML.

The FDA approval of Idhifa provides the first-ever treatment option for patients living with relapsed or refractory AML and an IDH2 mutation,” Mark Alles, CEO of Celgene, said in a company-issued release. “We appreciate the FDA’s efforts to expedite the availability of Idhifa for patients with this devastating disease weeks ahead of the PDUFA date. This milestone further illustrates the value of Celgene’s unique distributed research model. Our partnership with Agios is an exceptional example of how Celgene and its collaborators can positively impact the lives of patients with high unmet needs.”

An open-label, single-arm, multicenter, two-cohort clinical trial evaluated the efficacy of enasidenib in 199 patients with relapsed or refractory AML (median age, 68 years), who had IDH2 mutations as detected by the RealTime IDH2 Assay.

Patients received a starting dose of 100 mg enasidenib daily, and continued treatment for a minimum of 6 months, or until disease progression or unacceptable toxicity.

The percentage of patients with no evidence of disease and full recovery of blood counts after treatment and the percentage of patients with no evidence of disease and partial recovery of blood counts after treatment served as the primary endpoints.

Patients treated with enasidenib demonstrated a combined complete response or complete response with partial hematologic improvement rate of 23% (95% CI, 18-30) for a median duration of 8.2 months (95% CI, 4.3-19.4).

Among responders, median time to first response was 1.9 months (range, 0.5-7.5) and median time to best response was 3.7 months (range, 0.6-11.2). Eighty-five percent of these patients achieved combined complete response or complete response with partial hematologic improvement within 6 months of initiating therapy with enasidenib.

Of the 157 patients who required transfusions of blood or platelets at the start of the study, 53 (34%) no longer required transfusions during any 56-day postbaseline period.

Of the 42 patients who did not require transfusions of blood or platelets at baseline, 32 (76%) remained transfusion independent during any 56-day postbaseline period.


“The FDA approval of Idhifa just 4 years after entering the clinic is the first of what we expect to be multiple first-in-class precision medicines for patients with cancer and rare genetic diseases from our productive discovery engine,” David Schenkein, MD, CEO of Agios, said in the release. “We look forward to working closely with Celgene to co-commercialize Idhifa and provide access for patients in the U.S. with this devastating disease.”

Among the 214 patients evaluated for safety, median duration of exposure was 4.3 months (range, 0.3-23.6). The 30-day mortality rate was 4.1% and 60-day mortality rate was 11.7%.

The most common side effects included nausea, vomiting, diarrhea, increased levels of bilirubin and decreased appetite. The most common serious adverse events — which occurred in 77.1% of patients —included leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome and differentiation syndrome.

The FDA prescribing information includes a boxed warning for differentiation syndrome, which can be fatal if not treated. Fourteen percent of patients in the trial experienced differentiation syndrome.