AbbVie Announces Positive Results from Phase III VIALE-A (M15-656) Study of Venetoclax Combined with Azacitidine in Previously Untreated AML Patients Ineligible for Intensive Chemotherapy

AbbVie Announces Positive Results from the VIALE-A (M15-656) StudyThe study results demonstrated that treatment with venetoclax (VENCLEXTA or VENCLYXTO) in combination with azacitidine reduced the risk of death by 34% compared with azacitidine plus placebo in patients with previously untreated acute myeloid leukemia (AML) who were ineligible for intensive induction chemotherapy (hazard ratio [HR]=0.66 [95% CI, 0.52–0.85]; p=0.001). Patients treated with venetoclax in combination with azacitidine achieved an improvement in median overall survival (OS) (14.7 months in the venetoclax group vs. 9.6 months in the placebo group). A composite complete response (CR + CRi) was achieved in 66.4% of patients receiving venetoclax plus azacitidine, compared with 28.3% of those receiving azacitidine plus placebo.

Dr. Neil Gallagher, Chief Medical Officer of AbbVie, stated, “Patients with AML may be unable to tolerate chemotherapy due to the severity of their condition. Yet these patients face one of the most aggressive hematologic malignancies. The positive results from the VIALE-A study robustly demonstrate that venetoclax in combination with azacitidine significantly improves survival and complete remission rates in previously untreated patients.”

The randomized, double-blind, placebo-controlled, Phase III VIALE-A study evaluated the efficacy and safety of venetoclax in combination with azacitidine in patients with acute myeloid leukemia (AML) who were ineligible for standard induction therapy. The study met its primary endpoint, demonstrating statistically significant improvements in median overall survival (OS) and composite complete remission rate (CR + CRi). The primary endpoint in the United States and US reference countries was OS; the co-primary endpoints in China, Japan, the European Union (EU), and EU reference countries were OS and CR + CRi.

Dr. Courtney D. DiNardo, Professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and Principal Investigator, stated, “AML is a highly challenging hematologic malignancy to treat, with low patient survival rates, particularly among older patients who are ineligible for intensive induction chemotherapy, leaving them with limited treatment options. The results of the VIALE-A study further demonstrate that venetoclax in combination with azacitidine significantly prolongs overall survival and achieves superior response rates compared to azacitidine monotherapy. For previously untreated AML patients who are intolerant to chemotherapy, the combination of venetoclax and azacitidine represents an effective treatment option.”

This study also met its secondary endpoints, with a complete response (CR) rate of 36.7%, a CR with partial hematologic recovery (CRh) rate of 64.7%, and a composite complete response (CR + CRi) rate of 66.4% in the venetoclax combination therapy group; in the placebo group, the CR rate was 17.9%, the CRh rate was 22.8%, and the CR + CRi rate was 28.3%.

The safety profile observed in the venetoclax plus azacitidine group in this study was generally consistent with the known safety profiles of the two drugs when used as monotherapy.

Acute Myeloid Leukemia (AML) is one of the most common types of acute leukemia worldwide. It is estimated that 160,000 people globally are currently affected by this disease, with an incidence rate of 103 new cases per 100,000 individuals². AML is also among the most challenging hematologic malignancies to treat. Although existing diagnostic and therapeutic approaches have made certain advances, the 5-year survival rate for AML patients remains only approximately 28%. AML typically progresses rapidly, and due to factors such as age and comorbidities, not all patients can tolerate intensive induction chemotherapy.

It is reported that in November 2018, AbbVie received accelerated approval in the United States for venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are aged ≥75 years or have comorbidities that preclude the use of intensive induction chemotherapy. Furthermore, this indication has been approved in 19 countries and regions worldwide.