FDA Approves Combination Treatment for Acute Myeloid Leukemia

The US Food and Drug Administration (FDA) recently granted full approval of venetoclax (Venclexta) for treatment of newly diagnosed acute myeloid leukemia (AML).

The approval, granted to Genentech, is for use in combination with azacitidine, decitabine, or low-dose cytarabine, and is indicated for adults ≥75 years or who have comorbidities that prevent use of intensive induction chemotherapy.

The results of 2 Phase 3 confirmatory studies, VIALE-A and VIALE-C, lent support to this approval — VIALE-A showed that venetoclax plus azacitidine was superior to azacitidine alone in improving overall survival in newly diagnosed AML.

In the VIALE-A study, patients with confirmed AML who were ineligible for standard induction therapy were randomly assigned 2:1 to receive either azacitidine plus venetoclax or azactidiine plus placebo.

Azacitidine was administered subcutaneously or intravenously on days 1-7 every 28 days. Venetoclax or placebo was administered orally, once daily, every 28 days.

The primary endpoint for this study was survival.

Thus, at a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group—versus 9.6 months in the control group (HR, 0.66; 95% CI 0.52-0.85; P<.001).

Further, the incidence of complete remissions was higher in the azacitiidine-venetoclax group than in the control group (36.7% versus 17.9%, respectively; P<.001).

Notable key adverse events included nausea of any grade (44% azacitiidine-venetoclax, 35% control), grade 3 or higher thrombocytopenia (45% vs 38%), neutropenia (42% vs 28%), and febrile neutropenia (42% vs 19%). Infections of any grade occurred more frequenly in the azacitiidine-venetoclax group (84%) than in the control group (67%).

Additionally, serious adverse events occurred in 83% and 73%, respectively.

“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, M.D., Ph.D., chief medical officer and head of Global Product Development of Genentech in a statement.