The recent first global approval of enasidenib has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs, based on the development milestones tracked in AdisInsight.
In August 2017, enasidenib (Idhifa®), developed by Celgene Corp. (under a global, exclusive license from Agios Pharmaceuticals), received its first global approval in the US for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved companion diagnostic test.
Enasidenib is a first-in-class, small molecule, oral, targeted inhibitor of isocitrate dehydrogenase-2 (IDH2). IDH2 is one of two forms of an enzyme critical to the functioning of the citric acid cycle and cell metabolism; it is located in the mitochondria. Mutated forms of IDH produce elevated levels of 2-hydroxyglutarate (2-HG), an oncometabolite that may contribute to the formation and growth of malignancies. Mutations in IDH2 have been linked to the growth of various cancers, including AML. The companion diagnostic, the RealTime IDH2 Assay, developed by Abbott Laboratories, was FDA-approved at the same time as enasidenib.
The American Cancer Society states that an approximate 21,380 new cases of AML will be diagnosed during 2017, and of those, 10,590 cases (~50%) will be fatal; almost all will be in adults.
Enasidenib was granted priority review as well as Orphan Drug and Fast Track designations for the treatment of AML. The approval of the agent was based on clinical data from an open-label, single-arm, multicenter, two-cohort clinical trial of 199 adult patients with relapsed or refractory AML and an IDH2 mutation.
“The FDA approval of IDHIFA [enasidenib] just four 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, M.D., Chief Executive Officer of Agios.”
Martin Tallman, M.D., Hematologic Oncologist and Chief, Leukemia Service at Memorial Sloan Kettering Cancer Center further explained that, “AML is a complex, heterogeneous disease, which is particularly difficult to treat in the relapsed or refractory setting. IDH2 mutations inhibit the normal maturation of myeloid cells, so having a treatment that targets this mechanism is promising for patients and encouraging to us as physicians who have it as our goal to provide options for every patient.”
Enasidenib is also under various stages of development globally for AML, myelodysplastic syndromes and solid tumours.
Enasidenib carries a black boxed warning regarding the risks of developing Differentiation Syndrome, a fatal condition if not treated. This syndrome was observed in 14% of patients who received the agent during the clinical trial.
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