AbbVie Submits Regulatory Filing for Venetoclax Plus Azacitidine in Frontline AML Based on Phase 3 VIALE-A Trial Demonstrating Significant Overall Survival Benefit

Compiled by S.Li

On August 12 (local time), AbbVie announced that the results of the Phase 3 VIALE-A clinical trial were published in The New England Journal of Medicine (NEJM). The study evaluated the efficacy and safety of venetoclax in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive induction chemotherapy. The results demonstrated that, compared with azacitidine plus placebo, the venetoclax-based two-drug regimen significantly prolonged overall survival (OS) and reduced the risk of death by 34%.

VIALE-A is a two-arm, randomized, double-blind, international, multicenter Phase 3 clinical study that enrolled 433 patients with untreated acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. In the United States clinical research centers, overall survival (OS) was the sole primary endpoint. In China, Japan, and Europe, both the composite complete remission rate (CR+CRi) and OS served as co-primary endpoints. CR+CRi is a composite measure reflecting complete remission (CR) and complete remission with incomplete hematologic recovery (CRi).

The results showed that venetoclax in combination with azacitidine reduced the risk of death by 34% compared with placebo plus azacitidine (HR=0.66, 95% CI: 0.52–0.85; p<0.001). The median overall survival (OS) was 14.7 months (95% CI: 11.9–18.7) in the venetoclax combination group versus 9.6 months (95% CI: 7.4–12.7) in the placebo group. Furthermore, 66.4% of patients in the venetoclax combination group achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) (95% CI: 60.6–71.9), compared with only 28.3% in the placebo group (95% CI: 21.1–36.3), indicating a significantly higher response rate (p<0.001). Other secondary endpoints, including CR and CR with partial hematologic recovery, along with their analytical results, were published in the New England Journal of Medicine (NEJM).

The safety profile observed in the VIALE-A trial was consistent with the previously known safety profile of venetoclax in combination with azacitidine. The most common adverse reactions were hematologic toxicities and gastrointestinal disorders, including thrombocytopenia, nausea, constipation, neutropenia, febrile neutropenia, and diarrhea. The most frequently occurring serious adverse reactions were febrile neutropenia and pneumonia. Three patients in the venetoclax combination arm reported tumor lysis syndrome during the dose-escalation phase, whereas none were reported in the placebo arm.

Venetoclax was co-developed by AbbVie and Roche, with AbbVie and Roche’s Genentech jointly commercializing it in the United States and other regions worldwide. The drug has currently been approved for marketing in more than 50 countries and regions globally. In China, it has been included in the priority review pathway for hematologic malignancies.

The results of the VIALE-A trial were presented at the 25th European Hematology Association (EHA) Annual Congress held in June this year. AbbVie, in collaboration with Genentech, has submitted data from VIALE-A (M15-656), VIALE-C (M16-043), and the Phase 1/2 clinical studies M14-358 and M14-387 to the U.S. Food and Drug Administration (FDA) to seek accelerated approval for venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine for the treatment of patients aged 75 years or older with newly diagnosed acute myeloid leukemia (AML) who have comorbidities that preclude the use of intensive induction chemotherapy. AbbVie has also submitted these data to health authorities in other countries worldwide.

Reference Source: New England Journal of Medicine Publishes Positive Phase 3 Data of Venetoclax Combination in Acute Myeloid Leukemia (AML) Patients