The FDA has granted regular approval to venetoclax in combination with azacitidine, decitabine, or low dose cytarabine (LDAC) for newly diagnosed acute myeloid leukemia in adults aged 75 years or older who have comorbidities precluding intensive induction chemotherapy. Venetoclax was granted accelerated approval in November 2018, as well as priority review, breakthrough designation, and orphan drug designation.

“Today’s full approval is supported by the significant results that showed that Venclexta in combination with azacitidine extended overall survival for people with newly diagnosed acute myeloid leukemia who cannot tolerate intensive induction chemotherapy. We are very pleased that this application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this treatment option more rapidly to patients in the United States and other countries,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, in a press release.

Efficacy for this population was confirmed in 2 randomized, double-blind, placebo-controlled trials. In the VIALE-A trial, patients were randomized to receive either venetoclax plus azacitidine or placebo plus azacitidine. The median overall survival (OS) was 14.7 months in the venetoclax arm, compared with 9.6 months in the placebo arm. Patients treated with venetoclax also demonstrated an improvement in complete remission rates at 37% compared with 18% in the placebo group.

In the VIALE-C trial, patients were randomized to receive either venetoclax plus LDAC or placebo plus LDAC. The complete remission rate among patients who received venetoclax was 27% with a median duration of 11.1 months, compared with 7.4% in the placebo arm with a duration of 8.3 months. Venetoclax plus LDAC did not significantly improve OS in this study, according to a press release.

The most common adverse reactions of venetoclax in combination with either azacitidine, decitabine, or low dose cytarabine were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, and vomiting. The recommended dose depends on the combination regimen.

REFERENCE
FDA grants regular approval to venetoclax in combination for untreated acute myeloid leukemia [news release]. FDA; October 16, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-venetoclax-combination-untreated-acute-myeloid-leukemia. Accessed October 16, 2020.