Phase 1b Study of Investigational Treatment Venetoclax with Rituximab Shows Clinical Response in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

 - Preliminary findings showed 84 percent overall response rate in patients treated with investigational combination therapy 

- Six patients discontinued therapy after achieving a complete response (CR/CRi). Three patients maintained (CR/CRi) after a median of 12 months (0-21) 

NORTH CHICAGO, Illinois, June 12, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced updated results of a Phase 1b study that showed patients with relapsed/refractory chronic lymphocytic leukemia (CLL) taking venetoclax, an investigational B-cell lymphoma 2 (BCL-2) selective inhibitor, in combination with rituximab, had an overall response rate (ORR) of 84 percent (n=41/49).¹ Additionally, six patients stopped venetoclax after achieving either a complete response (CR) or CR with incomplete marrow recovery (CRi). Three patients maintained a response after a median of 12 months (0-21). These data were detailed in an oral presentation at the 20^th Congress of the European Hematology Association (EHA), June 11-15, in Vienna.

"Potentially, the most interesting part of these initial results is the data regarding the patients who have been able to come off treatment and who continue to maintain their complete response," said Professor Andrew W. Roberts, MBBS, FRACP, FRCPA, PhD, the Royal Melbourne Hospital Department of Clinical Hematology and Bone Marrow Transplant Service, Australia, and head of Clinical Translation at the Walter and Eliza Hall Institute of Medical Research. "The fact that this investigational venetoclax combination achieved these response rates suggests this treatment may offer patients another option and warrants further investigation."

CLL is the most common leukemia diagnosed in adults in western countries.² In the United States, CLL accounts for approximately 14,620 new cases of leukemia diagnosed each year.³ It is a slow-progressing cancer of the blood and bone marrow in which the bone marrow makes too many lymphocytes, a type of white blood cell that helps the body fight infection.⁴ The cause of CLL is unknown, though researchers believe it may be linked to a genetic mutation.

"AbbVie's goal is to develop treatments that can help patients with hard-to-treat cancers," said Gary Gordon, M.D., vice president, oncology development, AbbVie. "Combining the potential of venetoclax with rituximab is just one example of how we are investigating combination therapy."

About the Study – Abstract #S431
The Phase 1b, open-label, dose-escalation, multicenter, international study assessed the maximum tolerated dose and safety of venetoclax combined with rituximab in patients with relapsed/refractory CLL or small lymphocytic leukemia (SLL); secondary objectives included pharmacokinetics and preliminary efficacy.

Of the 49 patients evaluated, the overall response rate (ORR) was 84 percent (n=41/49), with 20 (41%) patients achieving a complete response (six patients achieved complete response with incomplete bone marrow recovery (CRi)), and 21 (43%) patients achieving a partial response (PR), one nodular.

The most common overall treatment emergent adverse events (AEs) (>25% patients) were neutropenia (53%), diarrhea and nausea (47%), upper respiratory tract infection (41%), pyrexia (37%) and fatigue, headache and cough (each 33%). Grade 3/4 treatment-emergent AEs (>10% patients) were neutropenia (51%), thrombocytopenia (16%) and anemia (14%). There was one treatment-emergent AE that led to death due to tumor lysis syndrome (TLS) and there were two treatment-emergent deaths after progressive disease (PD).

About Venetoclax 
Venetoclax is an investigational oral B-cell lymphoma-2 (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 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. In 2015, the FDA granted Breakthrough Therapy Designation to venetoclax for the treatment of CLL in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation. 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 Venetoclax (ABT-199 / GDC-0199) combined with rituximab induces deep responses in patients with relapsed/refractory chronic lymphocytic leukemia. Abstract S431. 20th Congress of the European Hematology Association (EHS) Meeting, Vienna 2015.
² Eichhorst, B. et al. "Chronic Lymphocytic Leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up." Annals of Oncology 22 (Supplement 6): vi50-vi54, 2011
³ American Cancer Society (2015) "Leukemia – Chronic Lymphocytic (CLL) Topics." http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics
⁴ American Cancer Society (2013) "Leukemia – Chronic Lymphocytic." http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf.