May 31, 2014

AbbVie Presents New Results from Studies of Investigational Oncology Compound ABT-199/GDC-0199 at the 2014 American Society of Clinical Oncology Annual Meeting

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- Data include results from two Phase I studies of ABT-199/GDC-0199 in relapsed/refractory chronic lymphocytic leukemia (CLL) and various subtypes of non-Hodgkin's lymphoma (NHL)

NORTH CHICAGO, Ill., May 31, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) released interim results from a Phase Ib clinical trial of ABT-199/GDC-0199, an investigational B-cell lymphoma 2 (BCL-2) selective inhibitor, in combination with rituximab (Abstract 7013). Results showed an overall response rate (ORR) of 84 percent, in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the most common leukemia in the United States. These results were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30June 3 in Chicago.

Of the 25 evaluable patients (who either completed the combination therapy or discontinued prior to completion), 36 percent (nine patients) achieved either a complete response or complete response with incomplete blood count recovery (CR/CRi) and 48 percent (12 patients) achieved a partial response (PR) as of April 16. Additionally, of the patients who achieved a CR, 75 percent (six patients) were identified as minimal residual disease (MRD) negative, indicating the detection of zero leukemic cells.

"The data presented at ASCO evaluating ABT-199/GDC-0199 in combination and as a single agent therapy in patients with a variety of tumors will help guide the continued development of this compound, which is being evaluated in pivotal Phase II and Phase III trials," said Gary Gordon, M.D., divisional vice president, oncology clinical development, AbbVie. "Patients suffering from these difficult-to-treat malignancies are the driving force behind the continued clinical development of ABT-199/GDC-0199."

Combination Trial with Rituximab Results Shows Response in Relapsed/Refractory Chronic Lymphocytic Leukemia (Abstract 7013)
The Phase Ib, open-label, multicenter, international trial of ABT-199/GDC-0199 administered in combination with rituximab in patients with relapsed/refractory CLL was designed to assess the safety of combination therapy, determine the maximum tolerated dose and establish a recommended Phase II dose. Secondary outcome measures included exploratory efficacy of the combination measured by tumor response or clinical disease progression. Additional objectives were to assess exploratory pharmacodynamics and pharmacogenetics of ABT-199/GDC-0199 in combination with rituximab by performing MRD assessments.

Out of 45 total patients enrolled in the trial, seven discontinued treatment during the study: five due to progression of disease (four Richter's transformation, one progressive CLL), one withdrew consent, and one death, as previously reported, due to fatal hyperkalemia, excessive potassium blood concentration, in the setting of clinical tumor lysis syndrome (TLS) at the first dose of 50 mg. The most common (? 25% of patients) treatment-emergent adverse events (AE) during the study were neutropenia (51%), nausea (38%) and diarrhea (33%). The most common serious adverse events were neutropenia (47%), thrombocytopenia (13%) and anemia (16%). The addition of rituximab to ABT-199/GDC-0199 has not resulted in new toxicities.

The combination of ABT-199/GDC-0199 and rituximab is being investigated in an ongoing Phase III clinical trial for the treatment of relapsed/refractory CLL.

Two-arm Monotherapy Trial Results Show Response in Relapsed/Refractory Chronic Lymphocytic Leukemia (Abstract 7015) and Various Subtypes of non-Hodgkin's Lymphoma (Abstract 8522)
Updated data from another Phase I study of ABT-199/GDC-0199 as a monotherapy included results from the trial arms investigating the compound as a treatment for patients with relapsed/refractory CLL and a variety of subtypes of non-Hodgkin's lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL). DLBCL is an aggressive type of lymphoma and the most common form of NHL, for which ABT-199/GDC-0199 received Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) earlier this year.

The Phase I, open-label, multicenter, international trial of ABT-199/GDC-0199 in patients with relapsed/refractory CLL and NHL was designed to assess the safety, determine the maximum tolerated dose and recommended Phase II dose, and evaluate pharmacokinetics. Secondary objectives included preliminary efficacy, including objective response rate (ORR), duration of response, time to progression, progression-free survival (PFS) and overall survival (OS).

"Patients with CLL and various subtypes of non-Hodgkin's lymphoma need additional options to help manage these difficult-to-treat cancers," said Matthew Davids, M.D., Medical Oncologist at Dana-Farber Cancer Institute in Boston and Instructor in Medicine, Harvard Medical School. "These results are exciting because they suggest ABT-199/GDC-0199 warrants further evaluation across several cancer patient groups."

As of April 9, 78 evaluable patients were enrolled in the CLL arm of the clinical trial; 19 patients had 17p deletion and 41 patients had fludarabine (F) - refractory CLL; both are considered high-risk subgroup patient populations of CLL. Due to concerns of TLS, the initial dose was reduced from 50 mg to 20 mg and daily dosing was modified to a weekly ramp-up period to the final dose of 400 mg. A ramp-up period with weekly dose increases occurred from 20, 50, 100, 200 mg to the final recommended Phase II dose (RPTD) of 400 mg.

The ORR was 77 percent, with 23 percent achieving CR. Of the 18 CR/CRi patients, 11 were evaluated for MRD and six were found to be MRD negative. The ORR for patients with 17p deletion and F-refractory CLL was 79 percent and 76 percent, respectively. The median duration of response has not been reached in the ongoing single agent Phase I study and continues to be evaluated.

ABT-199/GDC-0199 as a monotherapy in patients with relapsed/refractory CLL harboring the 17p deletion is under investigation in an ongoing Phase II clinical trial.

As of April 9, 62 patients were enrolled in the NHL arm of the trial, 20 (32%) with mantle cell lymphoma (MCL), 14 (23%) with follicular lymphoma (FL), 19 (31%) with DLBCL, four (7%) with Waldenstrom macroglobulinemia (WM), three (5%) with marginal zone lymphoma (MZL), one (2%) with primary mediastinal B-cell lymphoma (PMBCL) and one (2%) with multiple myeloma (MM). ABT-199/GDC-0199 was administered once-daily until disease progression or unacceptable toxicity. A two to three week lead-in period with a series of dose titration was implemented.

Two patients in the trial experienced a dose-limiting toxicity (grade 3 febrile neutropenia and grade 4 neutropenia) at the target dose of 600 mg. As previously reported, grade 3 TLS was seen after the initial dose in one patient with bulky MCL (elevations in phosphate and potassium only) and one patient with DLBCL (elevations in phosphate and uric acid only).

Results included an overall response rate of 48 percent for the 59 patients evaluable for efficacy. Of 19 MCL patients, 13 (68%) achieved a response, including one complete response; four of 13 patients with FL (28%) experienced a response; of 18 DLBCL patients, five (28%) achieved a response with one patient experiencing a complete response; three of four WM patients (75%) achieved a response and two of three MZL patients (67%) achieved a response with ABT-199/GDC-0199 as a monotherapy. Dose escalation continues to determine the maximum tolerated dose and RPTD.

The most common AEs (?20%) across the CLL and NHL arms of the monotherapy study, respectively, included nausea (35% and 37%), diarrhea (40% and 29%), fatigue (27% and 23%) and anemia (24% and 23%). Additional common AEs from the CLL arm of the monotherapy included upper respiratory tract infection (33%) and cough (20%). Grades 3/4 adverse events (?5% of patients) for the CLL and NHL arms, respectively, included neutropenia (33% and 10%), anemia (10% and 19%) and thrombocytopenia (7% and 7%). Additional grades 3/4 AEs from the CLL arm of the monotherapy study included febrile neutropenia (7%), hyperglycemia (7%), TLS (7%) and hypokalemia (5%). Discontinuations due to progressive disease and/or adverse events were reported in 37 of 105 patients enrolled in the CLL arm and in 39 of 62 enrolled patients in the NHL arm.

About ABT-199/GDC-0199
ABT-199/GDC-0199 is a selective inhibitor of B-cell lymphoma-2 (BCL-2) proteins. The B-cell lymphoma 2 gene prevents apoptosis of some cells including lymphocytes, and can be highly expressed in cancers in the lymph nodes, spleen, and other organs of the immune system. As a BH3-mimetic, ABT-199/GDC-0199 is designed to block the function of the BCL-2 protein by restoring the communication system that tells cancer cells to self-destruct. Jointly developed by AbbVie and Genentech, the companies are pioneering BCL-2 research with ABT-199/GDC-0199, which is currently in Phase III clinical trials for the treatment of CLL, the most common leukemia in the United States, and several other cancers. As an investigational drug, the safety and efficacy of ABT-199/GDC-0199 have not been established.

About Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States, accounting for a third of the cases diagnosed each year. 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. The cause of CLL is unknown, though researchers believe it may be linked to a genetic mutation.

About Non-Hodgkin's Lymphoma
Non-Hodgkin's lymphoma (NHL) includes a diverse group of blood cancers that originates in lymphocytes, a type of white blood cell that are part of the body's immune system. NHL is the most common hematological cancer, the fifth leading cause of cancer death and the second fastest growing form of cancer in the U.S. There are approximately 69,000 new cases of NHL diagnosed in the U.S. per year and 19,000 deaths are attributed to the disease annually.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma and the most common form of NHL, accounting for up to 30 percent of newly diagnosed cases and 60 percent of all aggressive types of lymphoma in the United States. Because DLBCL advances very quickly, it usually requires immediate treatment.

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, we are breaking ground in some of the most widespread and difficult-to-treat cancers, including multiple myeloma and chronic lymphocytic leukemia. Our 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 and our oncology portfolio, please visit

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.  AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.  For further information on the company and its people, portfolio and commitments, please visit  Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.



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