On 1 March, the FDA accepted Celgene and Agios’s New Drug Application (NDA) for the IDH2 inhibitor enasidenib (AG-221/CC-90007) for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase (IDH2) mutation. Under the Priority Review granted to the NDA, Celgene and Agios are expecting an accelerated approval from the FDA by 30 August 2017, which will set the stage for enasidenib to become the first IDH2 inhibitor indicated for the treatment of IDH2-mutated (IDH2+) AML.

Enasidenib’s clinical development program has been remarkably rapid, considering the lack of AML drug approvals by the FDA in the last decade. Agios, the drug’s discoverer, signed a deal with Celgene in 2010 to split the cost of development of enasidenib between the two companies, which significantly accelerated the drug’s clinical development program globally. The first clinical trial (NCT01915498) of enasidenib was initiated in June 2013 and by September 2015, 209 patients with IDH2+ advanced hematologic malignancies were treated with the single agent enasidenib in this study.

"Lack of effective and tolerable treatment options is a significant unmet need in AML."

The clinical data from 159 patients with relapsed/refractory IDH2+ AML treated in the Phase I/II trial form the basis of the NDA submission. Among this highly pretreated elderly (median age 69 years) patient population with a median of two prior lines of therapy, treatment with single agent enasidenib resulted in overall response and complete remission rates of 37% and 18%, respectively. Responses were durable with a median of 6.9 months and patients responding to the drug remained on treatment for up to 18 months (range of 1.8–18 months). While this study is ongoing, Celgene is conducting the Phase III IDHENTIFY trial (NCT02577406) which is only recruiting patients with IDH2+ relapsed/refractory AML and will provide further supporting evidence for enasidenib’s role in treating IDH2+ AML.    

Lack of effective and tolerable treatment options is a significant unmet need in AML, particularly in patients with relapsed/refractory disease. With the approval of enasidenib, about 10–15% of the AML population that harbors the IDH2 mutation will have an effective salvage treatment option. Despite being a niche segment, with a superior efficacy and safety profile, upon approval enasidenib is likely to become the new standard of care in the treatment of relapsed/refractory IDH2+ AML by rapidly displacing the currently available generic chemotherapy regimens.

Furthermore, two early-stage clinical trials (NCT02632708, NCT02677922) evaluating enasidenib in combination with standard of care regimens in newly diagnosed elderly patients with IDH2+ AML will lay the foundation for Celgene and Agios to seek label expansion to earlier treatment lines and maximize market share of the drug in IDH2+ AML. In the absence of other IDH2 inhibitors in late stage clinical development, GlobalData anticipates enasidenib will quickly establish a monopoly with initial market approval in relapsed/refractory disease followed by subsequent label expansion to the front-line treatment of patients with IDH2+ AML.