FDA Approves Idhifa for Relapsed or Refractory Acute Myeloid Leukemia

Drug targets mutations of IDH2 gene identified by new companion diagnostic test

The FDA has approved enasidenib (Idhifa, Celgene Corporation) for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) who have specific mutations in the IDH2 gene. The drug is approved for use with a companion diagnostic, the RealTime IDH2 Assay (Abbott Laboratories), which is used to detect the specific genetic mutations.

In certain patients, the use of enasidenib was associated with a complete remission and a reduction in the need for both red cell and platelet transfusions.

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of abnormal white blood cells in the bloodstream and bone marrow. The National Cancer Institute estimates that approximately 21,380 people will be diagnosed with AML this year; approximately 10,590 patients with AML will die of the disease in 2017.

Enasidenib is an isocitrate dehydrogenase-2 inhibitor that works by blocking several enzymes that promote cell growth. If the IDH2 mutation is detected in blood or bone marrow samples using the RealTime IDH2 Assay, the patient may be eligible for treatment with enasidenib.

The efficacy of enasidenib was studied in a single-arm trial of 199 patients with relapsed or refractory AML who had IDH2 mutations as detected by the RealTime IDH2 Assay. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission [CR]), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (CR with partial hematologic recovery [CRh]). With a minimum of six months of treatment, 19% of patients experienced CR for a median 8.2 months, and 4% of patients experienced CRh for a median 9.6 months. Of the 157 patients who required transfusions of blood or platelets due to AML at the start of the study, 34% no longer required transfusions after treatment with enasidenib.

Common side effects of enasidenib include nausea, vomiting, diarrhea, increased levels of bilirubin, and decreased appetite. Women who are pregnant or breastfeeding should not take enasidenib because it may cause harm to a developing fetus or a newborn baby.

The prescribing information for enasidenib includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can 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, doctors should treat patients with corticosteroids and monitor patients closely until symptoms go away.

Idhifa was granted priority review and orphan drug designations.

Source: FDA; August 1, 2017.