AbbVie Reports Phase 2 Results of Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia Patients with 17p Deletion

NORTH CHICAGO, Ill., Dec. 6, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced results of a Phase 2, open label trial studying investigational compound venetoclax in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and 17p deletion. In the trial, some patients were shown to respond to treatment, including complete remission (CR) and minimal residual disease negativity (MRD-).¹ The results from this trial, which was sponsored by AbbVie in collaboration with Genentech and Roche, were presented today during the 57th American Society of Hematology Annual Meeting (ASH) in Orlando, Florida.

The sponsors have submitted the data from this Phase 2 study of venetoclax, an investigational oral B-Cell Lymphoma-2 (BCL-2) inhibitor, to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of a New Drug Application (NDA) and a Marketing Authorization Application (MAA), respectively, in patients with relapsed/refractory CLL.

"The responses to monotherapy treatment with venetoclax are encouraging in these patients, who are among the most challenging to treat because they have CLL with 17p deletion," said Stephan Stilgenbauer, M.D., Ulm University, Germany, lead author on the study. "These results are consistent with the overall response rates observed in earlier studies, validating our research of venetoclax in relapsed/refractory CLL patients including those with the 17p deletion."

The data show venetoclax monotherapy achieved its primary endpoint with a 79.4 percent (n=85/107) overall response rate (ORR), with 84.7 percent having sustained duration of response (12 month estimate, overall median duration of response was not reached). In an exploratory endpoint assessing minimal residual disease negativity (MRD-) in 45 patients, MRD- of the peripheral blood was observed in 18 patients. More than 10 percent (10.3%) of all patients achieved independently assessed complete or partial response (at 12 months): 7.5 percent (n=8) complete response (CR) or CR with incomplete marrow recovery (CRi) and 2.8 percent (n=3) nodular partial response (nPR). Partial response (PR) was reported in 69.2 percent (n=74) of patients. Treatment-emergent adverse events (AEs) (all grades) in ≥20 percent of patients were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%) and fatigue (22%). Grade 3/4 AEs in ≥10 percent of patients were neutropenia (40%), anemia (18%) and thrombocytopenia (15%).   

"We are very encouraged by these results showing that venetoclax can achieve high rates of overall response in a difficult-to-treat patient population with relapsed/refractory CLL, such as those with 17p deletion," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "These encouraging results are part of our regulatory submission to the FDA and we are committed to working with FDA and EMA to deliver this treatment to appropriate patients."

About the Phase 2 Study
The Phase 2, multicenter, international, open label clinical trial was designed to evaluate the efficacy and safety of venetoclax monotherapy in 107 CLL patients with 17p deletion who relapsed or were refractory to existing therapies.

Patients with R/R del(17p) received venetoclax once daily with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over a period of five weeks with tumor lysis syndrome (TLS) prophylaxis. Patients were treated with daily 400 mg dosed continuously until disease progression or discontinuation for another reason. As of the interim data cut-off, (April 30, 2015) the median time on study was 12.1 (0.3-21.5) months.

Infection ≥ grade 3 occurred in 20 percent of patients. Laboratory TLS was reported in five patients, and all were manageable with electrolyte management and 1-day dose interruption (two patients). No clinical TLS events were reported.

There were 37 discontinuations: 22 due to progression of disease (nine Richter's transformation), nine due to AEs, two withdrew consent and one with non-compliance. In the trial, 11 deaths occurred (≤30 days from last dose of venetoclax): seven due to progressive disease and four due to AEs (stroke, liver derangement, septic shock and cardio-respiratory insufficiency).

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.² Approximately 3-10 percent of CLL patients have 17p deletion at diagnosis.³ The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent.⁴ Patients with the mutation have faster moving disease and poor outcomes.⁵ This mutation occurs in approximately 30-50 percent of patients with relapsed/refractory CLL.3 The median life expectancy of CLL patients with 17p deletion is less than 2-3 years.⁶

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 overexpressed 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 Stilgenbauer, S., et al (2015) "Venetoclax (ABT-199/GDC-0199) Monotherapy Induces Deep remissions, Including Complete Remission and Undetectable MRD, in Ultra-High Risk Relapsed/Refractory Chronic Lymphocytic Leukemia with 17p Deletion: Results of the Pivotal International Phase 2 Study." Presented at the Annual American Society of Hematology Annual Meeting
² American Cancer Society (2013) "Leukemia – Chronic Lymphocytic." http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.
³ 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.
⁴ Selner, L. et al. (2013) "What Do We Do with Chronic Lymphocytic Leukemia with 17p Deletion?" Curr Hemetol Malig Rep. 8(1):81-90.
⁵ 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.
⁶ 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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