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

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

- 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)

PR Newswire

NORTH CHICAGO, Ill., May 31, 2014

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 50^th Annual Meeting of the American Society of Clinical
Oncology (ASCO), May 30 – June 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."

CLL Arm
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.

NHL Arm
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 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. 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
www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebookor
LinkedIn page.

SOURCE AbbVie

Website: http://www.abbvie.com
Contact: David Freundel, (847) 937-4522; Investors: Liz Shea, (847) 935-2211
 
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