AbbVie Provides Update from Phase 3 Study Evaluating VENCLEXTA® (venetoclax) in Combination with Low-Dose Cytarabine in Newly-Diagnosed Patients with Acute Myeloid Leukemia (AML)

- Study did not demonstrate statistically significant improvement in the primary endpoint of overall survival (OS) (Hazard Ratio [HR]=0.75, [95% CI 0.52 - 1.07], p=0.11)

- At the time of the primary analysis median OS was 7.2 months in the venetoclax arm and 4.1 months in the comparator arm

- Results are indicative of clinical activity of venetoclax in combination with low-dose cytarabine

- AML is one of the most aggressive and difficult-to-treat blood cancers with a very low survival rate and few treatment options¹ ²

- Results will be published in a peer-reviewed journal and presented at an upcoming medical meeting

- Phase 3 VIALE-A trial evaluating venetoclax in combination with azacytidine is ongoing; at this time, indications for venetoclax remain unchanged

NORTH CHICAGO, IL, USA I February 28, 2020 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today 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.3

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]).3 Select secondary endpoints are included in the following table.

Select Secondary Endpoint Outcomes:*

Outcome Venetoclax plus LDAC
(n=143)
Placebo plus LDAC
(n=68)
Complete Remission 27.3% 7.4%
Complete Remission or Complete Remission with Incomplete Blood Count Recovery (CR + CRi) 47.6% 13.2%
Complete Remission or Complete Remission with Partial Hematologic Recovery (CR + CRh) 46.9% 14.7%
Complete Remission or Complete Remission with Incomplete Blood Count (CR + CRi) by Initiation of Cycle 2 34.3% 2.9%
*Nominal p values <0.001 

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.

Consistent with prior studies in AML, the most frequently reported AEs, irrespective of cause, were hematologic and are represented in the following table.

Serious and Non-Serious Adverse Events

  Venetoclax plus LDAC (n=142) Placebo plus LDAC (n=68)
AE's Non-Serious Serious Non-Serious Serious
Febrile neutropenia 15.5% 16.9% 11.8% 17.7%
Neutropenia 45.8% 2.8% 17.7% 0
Thrombocytopenia 40.9% 4.9% 36.8% 2.9%
Anemia 26.1% 2.8% 22.1% 0

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.4 AML typically worsens quickly and not all patients are eligible to receive intensive chemotherapy. Age and comorbidities are common factors limiting intensive therapy.5 Only approximately 28 percent of patients survive five years or more.6

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, 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.

AbbVie has a robust AML clinical research program and is continuing to explore the potential of venetoclax and other investigational medicines in AML with several studies, including VIALE-A, a Phase 3 study of venetoclax in combination with azacitidine compared to azacitidine plus placebo in newly-diagnosed patients who are ineligible for intensive chemotherapy.

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.

About the VIALE-C (M16-043) Phase 3 Trial
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.3 

About VENCLEXTA® (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.

VENCLEXTA is approved in more than 50 countries, including the U.S. AbbVie, in collaboration with Roche, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Uses and Important VENCLEXTA® (venetoclax) U.S. Safety Information7

Uses
VENCLEXTA is a prescription medicine used:

  • to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
  • in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
    • are 75 years of age or older, or
    • have other medical conditions that prevent the use of standard chemotherapy.

VENCLEXTA was approved based on response rates. Continued approval for this use may depend on the results of an ongoing study to find out how VENCLEXTA works over a longer period of time.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. AbbVie's oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 300 clinical trials and more than 20 different tumor types. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.

1 Döhner H, et al. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152.
2 American Cancer Society (2018). Typical Treatment of Most Types of Acute Myeloid Leukemia (Except Acute Promyelocytic M3). https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html.
3 Clinicaltrials.gov. NCT03069352: A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy.https://clinicaltrials.gov/ct2/show/results/NCT03069352. Accessed February 28, 2020.
4 American Cancer Society (2018). What is Acute Myeloid Leukemia (AML)? https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html
5 Pettit, K and Odenike, O. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies. Front Oncol. 2015; 5:250.
6 National Cancer Institute (2018). Acute Myeloid Leukemia - SEER Stat Fact Sheets. https://seer.cancer.gov/statfacts/html/amyl.html.
7 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.

SOURCE: AbbVie

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