FDA Approves Novel Oral Drug, Enasidenib (Idhifa), for AML Subset

Nick Mulcahy

August 01, 2017

The US Food and Drug Administration (FDA) has approved enasidenib (Idhifa, Celgene) for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) who have a specific genetic mutation.

Enasidenib is an oral targeted inhibitor of the isocitrate dehydrogenase-2 (IDH2) enzyme and is the first approved therapy for cases of relapsed or refractory AML with an IDH2 mutation, which is a small subset of patients with AML.

The drug is approved for use with a companion diagnostic, the RealTime IDH2 Assay (Abbott Laboratories), which is used to detect specific IDH2 gene mutations.

AML has had just one other drug approval, midostaurin (Rydapt, Novartis), since 1990.

"The use of [enasidenib] was associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a press statement.

The new targeted therapy fills an "unmet need" in this patient population, he added. Enasidenib works by blocking several enzymes that promote cancer cell growth.

The new approval is based on results from a single-group trial of 199 patients with relapsed or refractory AML with IDH2 mutations (detected by the RealTime IDH2 Assay).

The trial's posttreatment outcome measures included the percentage of patients with no evidence of disease and either full recovery of blood counts (ie, complete remission [CR]) or partial recovery of blood counts (ie, complete remission with partial hematologic recovery [CRh]).

After a minimum of 6 months of enasidenib treatment, 19% of patients experienced CR (median of 8.2 months), and 4% of patients experienced CRh (median of 9.6 months). Of the 157 patients who required transfusions of blood or platelets due to AML at the start of the study, one third (34%) no longer required transfusions after treatment with enasidenib.

Enasidenib's common adverse effects include nausea, vomiting, diarrhea, increased bilirubin levels, and decreased appetite.

The new drug is contraindicated in pregnant or breast-feeding women.

Enasidenib's prescribing information includes a boxed warning that differentiation syndrome can occur and be fatal if not treated.

Sign and symptoms of differentiation syndrome may include fever; dyspnea; acute respiratory distress; radiographic pulmonary infiltrates; pleural or pericardial effusions; rapid weight gain; peripheral edema; or hepatic, renal, or multiorgan dysfunction. At first suspicion of symptoms, patients should be treated with corticosteroids and be monitored closely until symptoms resolve.

The FDA had granted enasidenib priority review and orphan drug designations.

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