Idhifa (enasidenib), given alongside best supportive care, failed to prolong overall survival of older adults with relapsed or refractory acute myeloid leukemia (AML) carrying a mutation in the IDH2 gene, Phase 3 trial data show.
The main goal of the study, called IDHENTIFY (NCT02577406), was to determine if the combination of Idhifa and best supportive care would be superior to conventional treatments combining different chemotherapy agents with supportive care at prolonging the time these patients lived.
It evaluated Idhifa — an approved treatment for adults with advanced AML — in 319 patients, ages 60 and older, whose disease was refractory (resistant) to or who had relapsed after a second- or third-line therapy and who were positive for an IDH2 mutation.
Patients were randomly assigned to either Idhifa at 100 mg orally once daily, or to a conventional care regimen on continuous 28-day treatment cycles, for about seven months.
These regimens included best supportive care (BSC) only, azacitidine plus BSC, low-dose cytarabine plus BSC, or intermediate-dose cytarabine plus BSC.
Despite failing to meet the trial’s main goal, Idhifa’s safety profile was consistent with that reported in previous studies.
In light of these findings, Bristol Myers Squibb, the company now marketing Idhifa, stated it is planning to fully evaluate study data and will continue working with trial’s investigators to present detailed findings at an upcoming medical meeting.
“While we are disappointed by the outcome of the IDHENTIFY study, we remain confident in Idhifa’s established role as a treatment option for patients with relapsed or refractory AML with an IDH2 mutation and are grateful to all those who participated in the study,” Noah Berkowitz, MD, PhD, senior vice president of Global Clinical Development, and Hematology, at Bristol Myers Squibb, said in a press release.
“AML is one of the most difficult-to-treat blood cancers, and we’re committed to furthering our research and improving on the standards of care for patients living with this aggressive disease,” Berkowitz said.
Idhifa is the only FDA-approved therapy for patients with relapsed or refractory AML carrying a mutation in IDH2, which make up approximately 19% of all disease cases.
These mutations are thought to interfere with the process that allows immature blood cells to mature. As a result, instead of giving rise to healthy mature blood cells, young blood cells turn into malignant cancer cells.
Enasidenib, the therapy’s active ingredient, works by blocking the activity of the defective enzyme produced from the mutated copy of the IDH2 gene. By doing so, the therapy is expected not only to restore the normal process of blood cell differentiation, but also to inhibit the growth of existing cancer cells.
Idhifa has also been approved in Canada and Australia for the same indication.