AbbVie Announces New England Journal of Medicine Online Publication of Venetoclax Phase 1 Data in Relapsed/Refractory Chronic Lymphocytic Leukemia

NORTH CHICAGO, Ill., Dec. 6, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the online publication of new data in the New England Journal of Medicine (NEJM) showing some patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated with venetoclax experienced a response, including complete responses. The article reports data from Arm A of the study, in which all patients had relapsed CLL and more than one-third were refractory to their last treatment. Venetoclax is an investigational, first-in-class, B-cell lymphoma-2 (BCL-2) inhibitor being developed and commercialized by AbbVie and Genentech and Roche.

"Venetoclax is thought to inhibit the activity of BCL-2, an important anti-apoptotic protein," said Andrew W. Roberts, M.D., Department of Clinical Haematology and BMT, The Royal Melbourne Hospital, Parkville, Australia, and lead author on the NEJM paper. "In this arm of the dose-escalation study, we assessed safety and efficacy measures for venetoclax in patients with relapsed or refractory CLL."

In arm A of the M12-175 study, venetoclax had an overall response rate of 79 percent (n=92/116) and complete response in 20 percent of patients. Serious adverse events (AEs) occurring in ≥ 2 percent of patients were febrile neutropenia, pneumonia, immune thrombocytopenia, tumor lysis syndrome, diarrhea, fluid overload, hyperglycemia, prostate cancer, pyrexia, upper respiratory tract infection, and viral upper respiratory tract infection. Grade 3 or 4 AEs occurring in ≥ 2 percentof patients were diarrhea, nausea, neutropenia, fatigue, anemia, thrombocytopenia, vomiting and hyperglycemia.

"The publication of these data is the culmination of nearly two decades of work by AbbVie scientists who have advanced our understanding of the BCL protein family and its role in certain cancers," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "Results from this Phase 1 study provide important information about how we might treat relapsed/refractory CLL and about the potential of venetoclax to provide responses for patients battling the disease."

About the Study 
The paper, titled "Targeting BCL-2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia" (Roberts et al, N Engl J Med 2015: published December 6, 2015), reported data from one arm of a first-in-human, Phase 1, open-label, multicentre, dose-escalation study of venetoclax in relapsed or refractory CLL/small lymphocytic lymphoma (SLL). The primary objectives of the study were to determine the safety profile, pharmacokinetics, and maximum tolerated dose. Secondary objectives were to assess response rates and other measures of efficacy. In the initial dose-escalation phase, all 56 patients received active treatment in one of eight dose cohorts (150-1200mg/day). Sixty additional patients were treated in an expansion cohort with a weekly stepwise ramp-up in dosing to 400mg/day. Patients continued daily venetoclax until disease progression or unacceptable toxicity.

About Chronic Lymphocytic Leukemia (CLL) and 17p Deletion 
CLL is a typically slow-progressing cancer of the bone marrow and blood in which the bone marrow makes too many lymphocytes, a type of white blood cell.¹ Approximately 3-10 percent of CLL patients have 17p deletion at diagnosis.² The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent.³ Patients with the mutation have faster moving disease and poor outcomes.⁴ This mutation occurs in approximately 30-50 patients with relapsed/refractory CLL. The median life expectancy of CLL patients with 17p deletion is less than 2-3 years.⁵

About Venetoclax   
Venetoclax is an investigational oral BCL-2 inhibitor being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be over expressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is being developed in collaboration with Genentech and Roche. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

About AbbVie Oncology  
AbbVie's oncology research is focused on the discovery and development of targeted therapies that work against the processes cancers need to survive. By investing in new technologies and approaches, AbbVie is breaking ground in some of the most widespread and difficult-to-treat cancers, including glioblastoma multiforme, multiple myeloma and chronic lymphocytic leukemia. AbbVie's oncology pipeline includes multiple new molecules in clinical trials being studied in more than 15 different cancers and tumor types. For more information on AbbVie Oncology, please visit http://oncology.abbvie.com.

About AbbVie 
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements 
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, the likelihood that the transaction is consummated, the expected benefits of the transaction, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

¹ American Cancer Society (2013) "Leukemia – Chronic Lymphocytic." http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf.
² Schnaiter, A. et al. (2013) "17p Deletion in Chronic Lymphocytic Leukemia: Risk Stratification and Therapeutic Approach."  Hematol Oncol Clin N Am 27 (2013) 289–301.
³ Selner, L. et al. (2013) "What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?" Curr Hemetol Malig Rep. 8(1):81-90. 
⁴ Jain, N, and O'Brien, S, (2012) "Chronic Lymphocytic Leukemia with Deletion 17p: Emerging Treatment Options." Oncology. 26:11. http://www.cancernetwork.com/leukemia/content/article/10165/2112686.
⁵ Stilgenbauer, S, and Zenz, T, (2010) "Understanding and Managing Ultra High-Risk Chronic Lymphocytic Leukemia." ASH Education Book. 2010(1):481-488.

SOURCE AbbVie

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