On June 4, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that encouraging new data from a Phase 1 study evaluating ivosidenib (AG-120) or enasidenib (IDHIFA; AG-221) in combination with azacitidine in newly diagnosed isocitrate dehydrogenase (IDH) mutant acute myeloid leukemia (AML) patients (Press release, Agios Pharmaceuticals, JUN 4, 2018, View Source [SID1234527119]). The data were featured at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"Patients with newly diagnosed AML who are ineligible for intensive "7+3" chemotherapy typically have poor outcomes and few available treatment options," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "With additional patients now treated in the ivosidenib arm of this Phase 1 study, the updated combination data demonstrate a favorable safety profile and impressive response rates vs. those expected with azacitidine alone. I look forward to further demonstrating the clinical benefit of utilizing an IDH inhibitor in combination with traditional frontline AML treatment as part of the ongoing Phase 1 and randomized trials."

About the Ongoing Phase 1/2 Study
The ongoing Phase 1/2 study is evaluating an investigational use of enasidenib or ivosidenib in combination with azacitidine in patients with newly diagnosed IDH mutant AML unable to receive intensive chemotherapy. In the Phase 1b portion of the study, 23 patients received 500 mg of ivosidenib daily plus azacitidine and 6 patients received enasidenib (n=3 at 100 mg and n=3 at 200mg) daily plus azacitidine.

As of the March 15, 2018 data cutoff, 19 patients remained on study (17 ivosidenib, 2 enasidenib).
Enrollment is complete for the ivosidenib Phase 1b portion. Enasidenib and azacitidine continue to be assessed in the randomized Phase 2 portion of the study.
Ivosidenib Results
Safety

The most common adverse events (AEs) regardless of causality were nausea (61%, n=14), anemia (52%, n=12) and thrombocytopenia (48%, n=11).
The most common Grade 3-4 AEs were anemia and thrombocytopenia (44%, n=10 each), and febrile neutropenia (39%, n=9).
IDH differentiation syndrome was reported in three patients.
Efficacy

Overall, 78% of patients (18/23) had a response
The combined CR/CRi/CRp rate was 65% (15/23).

44% (10 of 23 patients) had a complete response (CR)
22% (5 of 23 patients) had a complete response with incomplete hematologic or platelet recovery (CRi/CRp)
All patients with a CR, CRi or CRp response remain on treatment as of the data cutoff with patients on study up to 19 months. The median duration of response has not been reach .
The median time to first response was 1.8 months (range 0.7-3.8 months) and the median time to best response was 3.6 months (range 0.8-6.7 months).
IDH1 mutation clearance was observed in 7 of 21 patients with available longitudinal VAF profiling

Enasidenib Results
Updated data from the six patients in the enasidenib and azacitidine combination presented in December 2017 were also shown.

Safety

The most common AEs regardless of causality were hyperbilirubinemia (n=5) and abdominal pain, nausea, vomiting and pyrexia (n=4 each).
The most common Grade 3-4 AEs were anemia and thrombocytopenia (n=3 each) followed by hyperbilirubinemia, neutropenia, lung infection and pneumonia (n=2 each).
Efficacy

Overall, four out of six patients achieved a response, including 3 CRs and one MLFS.
IDH2 mutation clearance was observed in 3 of 6 patients with available longitudinal VAF profiling
Neither enasidenib nor ivosidenib are approved in any country for the treatment of patients with newly diagnosed AML or approved in combination with azacitidine.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age of diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.