VENCLEXTA, Low-Dose Cytarabine Combination Study for AML Does Not Meet Primary Endpoint

AbbVie announced the VIALE-C (M16-043) trial of venetoclax (VENCLEXTA®) in combination with low-dose cytarabine (LDAC) versus LDAC in combination with placebo did not meet its primary endpoint of statistically significant improvement of overall survival (OS) for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy at the time of the planned analysis.

Treatment with the venetoclax combination showed a 25% reduction in the risk of death compared to LDAC with placebo (Hazard Ratio [HR]=0.75 [95% CI 0.52–1.07], p=0.11). The venetoclax with LDAC arm also showed a median OS of 7.2 months vs. 4.1 months in the LDAC arm alone. A post-hoc analysis after an additional six months of follow up showed an increase in median OS of 8.4 months in the venetoclax plus LDAC arm and 4.1 months in the placebo plus LDAC arm (HR=0.70 [95% CI 0.50-0.99]).

The safety profile of the combination is consistent with the safety results reported in the Phase 1/2 studies that supported the U.S. Food and Drug Administration (FDA) approval of the combination. At this time, indications for venetoclax remain unchanged.

"We remain committed to AML patients and our research in AML and other blood cancers," said Neil Gallagher, M.D., Ph.D., chief medical officer and vice president of development, AbbVie. "The study results, while not statistically significant, are indicative of the clinical activity of venetoclax in combination with low-dose cytarabine."

The VIALE-C study evaluated venetoclax in combination with LDAC compared with LDAC alone in newly-diagnosed patients with AML who are ineligible for intensive chemotherapy. The median follow-up time at the end of the planned primary analysis for both arms of the trial was 12 months. Select secondary endpoints that were evaluated in the primary analysis included remission rates, transfusion independence, and event-free survival.

AML is one of the most difficult-to-treat blood cancers. It forms in the bone marrow and results in increasing numbers of abnormal white blood cells in the bloodstream and bone marrow. AML typically worsens quickly and not all patients are eligible to receive intensive chemotherapy. Age and comorbidities are common factors limiting intensive therapy. Only approximately 28 percent of patients survive five years or more.

In November 2018, AbbVie received accelerated approval for VENCLEXTA in the U.S. in combination with azacitidine, decitabine, or LDAC for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy based on Phase 1/2 studies. Continued approval for this indication may be contingent upon verification and description of clinical benefit in an ongoing trial. Approval was also granted in Mexico, Israel, Puerto Rico, Peru, Brazil, Russia, Argentina, Guatemala, Uruguay, Lebanon, Bahrain, Kazakhstan, Panama, Saudi Arabia, Taiwan, China, Australia, and United Arab Emirates. AbbVie has provided the results from VIALE-C to the FDA and other global health authorities and will continue to work with them to ensure that venetoclax remains an appropriately managed option for patients with AML.

VENCLEXTA 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 total of 211 treatment-naïve AML patients were enrolled and 210 were treated in the randomized, double-blind, placebo-controlled Phase 3 VIALE-C trial. The trial was designed to evaluate the efficacy and safety of venetoclax in combination with low dose cytarabine (LDAC) (N=143) compared with placebo in combination with LDAC (N=68). The primary efficacy endpoint was overall survival (OS) compared between the groups of patients receiving LDAC and those who received LDAC with venetoclax.

VENCLEXTA® (venetoclax) 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. VENCLEXTA targets the BCL-2 protein and works to help restore the process of apoptosis.

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