Leukemia
AG-221 Clinical Results
Promise “Revolutionary”
Approach in AML
IDH2 mutations represent new
therapeutic target
Early clinical findings with AG-221 – a first-in-class potent,
selective oral inhibitor of mutated isocitrate dehydrogenase 2 (IDH2) – reveal durable responses, including complete remissions, in patients with advanced hematologic
malignancies associated with IDH2 mutations.
Approximately 15 percent of patients with acute myeloid leukemia
(AML) harbor a mutation of either the IDH1 or IDH2 gene. These
somatic mutations in IDH1 and IDH2 confer gain-of-function
activity in cancer cells, noted lead AG-221 study author Eytan
M. Stein, MD, assisting attending physician at Memorial Sloan
Kettering Cancer Center, in an oral presentation at the 2014 ASH
Annual Meeting. The genetic abnormality leads to altered enzyme
activity and increased production of the oncometabolite 2-hydroxyglutarate (2-HG), which alters epigenetic patterns and prevents
differentiation of immature white blood cells. AG-221 works by
inhibiting the mutated IDH2 enzyme and eliminating production
of 2-HG.
“I am extremely enthusiastic about the data to date,” Dr. Stein
said. “The early results with AG-221 are truly remarkable for a
population with relapsed and refractory AML.”
Dr. Stein presented data from 73 patients enrolled in the ongoing first-in-human, phase 1, open-label, dose-escalation study of
AG-221. Of the 73 patients, 55 have relapsed/refractory AML and
13 have undergone prior bone marro