June 03, 2013
AbbVie Presents Results from Phase I Study of Investigational Oncology Compound ABT-199 at American Society of Clinical Oncology Annual Meeting
Data in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma
Enrollment in Clinical Trials for ABT-199 Continues

NORTH CHICAGO, Ill., June 3, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced results from a Phase I study of ABT-199, an investigational BCL-2 (B-cell lymphoma 2) selective inhibitor, for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the most common leukemia in the United States, and relapsed/refractory non-Hodgkin's lymphoma (NHL).  Results from the study were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).

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

"The ABT-199 data underscore AbbVie's commitment to the development of treatments for some of the hardest-to-treat cancers like CLL and NHL," said Gary Gordon, M.D., divisional vice president, oncology clinical development, AbbVie. "Early trials of ABT-199 have shown the compound's potential in these hematological malignancies, which support the continuation of its clinical development program."

As of April 2013, 56 patients have enrolled in the CLL arm of the Phase I trial, and 40 patients are currently active. Study participants were given a single oral dose of ABT-199, followed by six days without medication, before continuous once-daily dosing. Due to concerns over tumor lysis syndrome (TLS), the initial dose was reduced and daily dosing was modified. Single-agent activity was observed in the trial and warrants further single-agent and combination trials evaluating ABT-199 in patients with CLL. Dose and schedule evaluation will continue.

"While still early in the development process, the activity with ABT-199 as a single-agent supports further investigation of the compound in patients with CLL, a patient population with a high unmet need for new treatment options," said Matthew Davids, M.D., attending physician in the Lymphoma Program of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, and Instructor in Medicine at Harvard Medical School.

During the study, 13 patients discontinued treatment; seven due to progression of disease and six for other reasons (two due to TLS, two for other illnesses, one for thromboembolic event and one consent withdrawal). The most common non-hematological adverse events (AEs) during the study were nausea (36%), diarrhea (30%), fatigue (25%), upper respiratory tract infection (23%) and cough (16%). In the first study group, TLS occurred in all three of the enrolled patients; once the modified dosing schedule was utilized, three of the 53 patients experienced adverse events of TLS. One fatal adverse event occurred in a patient with laboratory evidence of TLS.

Preliminary efficacy results showed that 46 of 55 patients (84%) achieved a response to ABT-199.  Specifically, ten patients (18%) achieved a complete response (CR) or complete response with incomplete bone marrow recovery and 36 patients (65%) achieved a partial response (PR). The study also demonstrated a response in patients with high-risk markers. A partial response was achieved by 13 of 16 patients with deletion of the short arm of chromosome 17 (17p deletion) and 14 of 18 patients with fludarabine-refractory CLL.  Later stage clinical trials are expected. 

As of April 2013, 32 patients have enrolled in the NHL arm of the trial, and 12 are currently active. Patients were given a single oral dose (50-400mg) followed by six days without medication before being dosed with continuous once-daily dosing. Due to concerns over TLS, a dose-escalation protocol was implemented. Patients who were treated with up to 900mg have been evaluated to date. Single-agent activity was observed in the trial and warrants further clinical investigation. Dose escalation will continue to determine maximum-tolerated dose and optimal dosing regimen.

The most common AEs (≥15% of patients) were nausea (36%), diarrhea (26%), dyspepsia, vomiting, fatigue, pyrexia and cough (16% each). Grade 3/4 AEs occurring in more than one patient were anemia, neutropenia (four patients each), febrile neutropenia (two patients) and thrombocytopenia (three patients). Grade 3/4 thrombocytopenia was not dose dependent. Grade 3 TLS was seen after the initial dose in one patient with bulky MCL (>10 cm). With a median follow-up of five months (range 0.5-15), 17 patients have discontinued: 13 due to progression of disease, two due to AEs and two proceeded to bone marrow transplant (BMT) in ongoing response. 

Preliminary efficacy results showed 17 of 32 patients (53%) achieved an overall response rate (ORR), with one patient experiencing a complete response and 15 patients experiencing a partial response.  Studies are ongoing.

About ABT-199/GDC-0199
ABT-199 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 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, which is currently in Phase 1/1b clinical trials for the treatment of CLL, the most common leukemia in the United States, and several other cancers.

The U.S. Food and Drug Administration (FDA) recently accepted AbbVie's amended clinical trial protocols for studies of ABT-199 in patients with CLL and enrollment for ABT-199 clinical trials in CLL, NHL and multiple myeloma has been re-instated. AbbVie and Genentech expect to move ABT-199 into later-stage clinical trials in the near future. 

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.

Mantle cell lymphoma (MCL) is an aggressive, rapidly progressive subtype of NHL, and is not curable with standard treatment. The median life expectancy for a patient with MCL following first relapse is one to two years.

About AbbVie Oncology
The fight against cancer is one of the greatest battles in medicine and the varied nature of the disease requires a diverse approach that looks at multiple disease targets in a variety of tumor types. 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.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. 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. In 2013, AbbVie employs approximately 21,000 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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