Results from the Phase III VIALE-A trial (M15-656; NCT02993523) of venetoclax (Venclexta®; AbbVie/Genentech) in combination with azacitidine (Vidaza®) versus azacitidine in combination with placebo demonstrated statistically significant improvement in the primary endpoints of overall survival (OS) and composite complete remission rate (CR + CRi), meeting is dual endpoints for patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.
Venetoclaxa is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. Venetoclaxa targets the BCL-2 protein and works to help restore the process of apoptosis.
At the recommendation of an independent data monitoring committee (IDMC), and per the prespecified interim analysis plan, due to positive efficacy results, the trial results will be reported early, and the data from the trial will be submitted to the U.S. Food and Drug Administration and other regulatory authorities around the globe.
Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is one of the most aggressive and difficult-to-treat blood cancers with a very low survival rate and limited treatment options.  Despite advances in available therapies and care, the 5-year survival rate for patients diagnosed with AML remains approximately 28%. 
The disease typically worsens quickly, and due to age and comorbidities, not all patients are eligible to receive intensive chemotherapy. The positive results from VIALE-A support the clinical benefit of the venetoclax plus azacitidine combination for these patients with AML who are ineligible for intensive chemotherapy.
AML is the most common acute leukemia in the world. An estimated 160,000 people are currently living with the disease globally with an incidence rate of 103 new cases per 100,000 people.
The full trial results will be presented at a future medical meeting and published in a peer-reviewed journal.
“For the past three decades, there have been few options for patients with AML who cannot receive or tolerate intensive chemotherapy or a bone marrow transplant,” said Neil Gallagher, M.D., Ph.D., chief medical officer and vice president of development, AbbVie.
“The positive results from VIALE-A support the clinical benefit of the venetoclax plus azacitidine combination in patients with AML who are ineligible for intensive chemotherapy and reflect our ongoing commitment to transform the standards of care for patients with hematologic malignancies,” Gallagher added.
Efficacy and safety
The observed safety profile is generally consistent with the known safety profile of venetoclax combined with azacitidine as observed in the previous Phase I/II studies and the known safety profiles of the two medications.
The double-blind, placebo-controlled Phase III VIALE-A trial (M15-656; NCT02993523) enrolled and randomized 443 treatment-naïve AML patients. The trial was designed to evaluate the efficacy and safety of venetoclax in combination with azacitidine (n=287) compared with placebo in combination with azacitidine (n=146).
In November 2018, AbbVie received accelerated approval in the U.S. for venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy based on Phase I/II studies.
The Phase III VIALE-A and VIALE-C (M16-043) studies were conducted as confirmatory trials following the accelerated U.S. FDA approval of venetoclax in AML in 2018. In February 2020, AbbVie provided an update on the Phase III VIALE-C study of venetoclax in combination with LDAC compared with LDAC in combination with placebo.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.
A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy – NCT02993523
A Safety and Efficacy Study of Oral Venetoclax Tablets and Injectable Azacitidine Versus Best Supportive Care as Maintenance Therapy in Adult Participants With Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy to Evaluate Improvement in Relapse-Free Survival (VIALE-M) – NCT04102020
A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML) (VIALE-T) – NCT04161885
A Study of the Effectiveness of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in Patients With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy – NCT03941964
NDC Code: 0074-0576 [Info]
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