Enasidenib (Idhifa), developed by Celgene and Agios, has been granted FDA approval in tandem with a companion diagnostic test to detect IDH-2 mutations.
An oral targeted therapy that can be used in patients with relapsed/refractory acute myeloid leukemia (AML) who carry a mutation in the isocitrate dehydrogenase-2 (IDH2) enzyme has been approved. Enasidenib (Idhifa), developed by Celgene and Agios, has been granted FDA approval in tandem with a companion diagnostic test to detect IDH-2 mutations.
Detected in 8% to 19% of AML patients, the IDH2 mutation blocks normal blood cell development and results in an overabundance of immature blood cells in individuals. IDH2, an enzyme active in the citric acid cycle, is a very active metabolic enzyme, and mutations in the gene are associated with the development of AML, glioma, chondrosarcoma, intrahepatic cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma cancers.
Efficacy data evaluated by the FDA for the current approval included a single-arm study with 199 patients who had relapsed/refractory AML and carried an IDH2 mutation, detected in their blood or bone marrow sample using the RealTime IDH2 assay, developed by Abbott Laboratories. Patients (median age, 68 years) had received between 1 and 6 previous treatments, and 52% were refractory to prior care. In the current study, they were administered 100 mg enasidenib daily, until disease progression or unacceptable toxicity was noted.
The endpoint being measured was no evidence of disease and full recovery of blood counts following treatment. After 6-months on enasidenib, 19% of patients experienced complete remission for a median duration of 8.2 months, while 4% of patients experienced complete remission with partial hematologic recovery for a median 9.6 months.
Thirty-four percent patients who needed blood or platelet transfusion (n = 157) no longer required the procedure following treatment with enasidenib during a 56-day post-baseline period. Of the remaining 42 patients who were transfusion-free at baseline, 76% (n = 32) remained so during the 56-day post-baseline period.
A safety evaluation was conducted in 214 patients, with a median duration of exposure of 4.3 months. The 30-day and 60-day mortality rates with enasidenib were 4.2% (9/214) and 11.7% (25/214), respectively. Common treatment-associated side effects include nausea, vomiting, diarrhea, increased levels of bilirubin, and decreased appetite. The drug is contraindicated in pregnant or breastfeeding women.
“We appreciate the FDA’s efforts to expedite the availability of Idhifa for patients with this devastating disease weeks ahead of the [Prescription Drug User Fee Act] date,” said Mark Alles, CEO of Celgene.
“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,” said David Schenkein, MD, CEO of Agios, which has co-developed the drug with Celgene. “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.”