AbbVie Presents Preliminary Results from Phase I Study of Investigational Oncology Compound ABT-199/GDC-0199 in Patients with

  AbbVie Presents Preliminary Results from Phase I Study of Investigational
    Oncology Compound ABT-199/GDC-0199 in Patients with High-Risk Chronic
 Lymphocytic Leukemia (CLL) at European Hematology Association Annual Meeting

Analysis Evaluates Response Rates in Patients with 17p Deletion,
Fludarabine-Refractory CLL

Data in Patients with Mantle Cell Lymphoma (MCL) Also Presented

PR Newswire

NORTH CHICAGO, Ill., June 17, 2013

NORTH CHICAGO, Ill., June 17, 2013 /PRNewswire/ --AbbVie (NYSE: ABBV) today
announced preliminary results from a Phase I study of ABT-199/GDC-0199, an
investigational BCL-2 (B-cell lymphoma 2) selective inhibitor, in patients
with high-risk relapsed/refractory chronic lymphocytic leukemia (CLL), and in
patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). High-risk CLL
patients are those with deletions of chromosome 17p or whose disease is
refractory to fludarabine therapy. These data were presented at the 18^th
Congress of the European Hematology Association (EHA) in Stockholm, Sweden.

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/GDC-0199 in patients
with relapsed/refractory CLL and NHL. Secondary objectives included
preliminary efficacy, including objective response rate, duration of response,
time to progression, progression-free survival and overall survival.

"New treatment options are critically needed for patients with hard-to-treat
cancers including high risk CLL and MCL," said Gary Gordon, M.D., divisional
vice president, oncology clinical development, AbbVie. "The preliminary data
presented at EHA further support the ongoing clinical trial program for
ABT-199/GDC-0199 via the BCL-2 pathway."

CLL Arm
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/GDC-0199, 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/GDC-0199 in patients
with CLL. Dose and schedule evaluation will continue.

Of the 56 patients enrolled, 34 were considered high-risk CLL patients – those
with deletions of chromosome 17p or whose disease is refractory to fludarabine
therapy. In the post-hoc analysis to determine if high-risk CLL patients could
have similar response rates to the overall study population, 17 (30%) patients
had 17p deletion and 18 (32%) had fludarabine-refractory CLL.

"High-risk CLL patients are a challenging subgroup to treat, as they tend to
have disappointing results with conventional chemotherapy regimens," said
Professor Andrew Roberts, Hematologist at the Royal Melbourne Hospital and
head of Clinical Translation at the Walter and Eliza Hall Institute of Medical
Research, Melbourne, Australia. "While still early in the development
process, preliminary response rates observed in these patients appear similar
to those observed in other CLL patients being treated with ABT-199/GDC-0199.
These data justify further investigation of this compound in patients with 17p
deletion and fludarabine-refractory CLL."

During the study, 16 patients discontinued treatment; nine due to progressed
disease and seven for other reasons (two due to TLS, three for other
illnesses, one for thromboembolic event and one consent withdrawal). The most
common hematological adverse events (AEs) during the study were neutropenia
(39%), thrombocytopenia (18%) and anemia (13%). The most common
non-hematological AEs were diarrhea (41%), nausea (38%), fatigue (29%), upper
respiratory tract infection (27%) and cough (23%). 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 TLS, one of which
was a fatal AE that occurred within dose escalation to 1200mg.

Preliminary efficacy results demonstrated that 13 of 16 evaluable patients
(81%) with 17p deletion achieved a response to ABT-199/GDC-0199. Specifically,
2 patients (12%) achieved a complete response (CR) or complete response with
incomplete bone marrow recovery and 11 patients (69%) achieved a partial
response (PR). Among the patients with F-refractory CLL, 14 of 18 evaluable
patients (78%) achieved a response; 3 (17%) achieved a complete response or
complete response with incomplete bone marrow recovery and 11 (61%) achieved a
partial response. These results are similar to the preliminary efficacy
observed in the overall CLL study population (84 percent response rate).
Further clinical studies to evaluate the efficacy and safety of
ABT-199/GDC-0199 in CLL, and specifically in patients with high-risk CLL, are
necessary.

NHL Arm
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 hematological AEs during the study were neutropenia,
thrombocytopenia (16% each), and anemia (13%). The most common
non-hematological AEs were nausea (41%), diarrhea (28%), dyspepsia, vomiting,
fatigue, pyrexia, upper respiratory tract infection and cough (19% each).
Grade 3/4 thrombocytopenia, neutropenia and anemia occurred in four patients
(13% each). Grade 3/4 thrombocytopenia was not dose dependent. TLS was seen
after the initial dose in one patient with bulky mantle cell lymphoma (MCL)
(>10 cm). With a median follow-up of five months (range 0.5-15), 17 patients
discontinued: 13 due to progression of disease, two due to AEs and two
proceeded to bone marrow transplant in ongoing response.

Of the patients enrolled in this arm of the trial, eight (26%) had MCL, an
aggressive, rapidly progressive subtype of NHL that does not respond well to
current therapies. Preliminary efficacy results showed that all eight patients
(100%) with MCL achieved a partial response. Further clinical studies to
evaluate the efficacy and safety of ABT-199/GDC-0199 in MCL are necessary.

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 (death) 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.
ABT-199/GDC-0199 is being developed in collaboration with Genentech in the
United States and Roche outside the United States. Together, the companies are
pioneering BCL-2 research with ABT-199/GDC-0199, which is currently in Phase
1/1b clinical trials for the treatment of CLL and several other cancers.

Enrollment is currently active in ABT-199/GDC-0199 clinical trials in CLL, NHL
and multiple myeloma. AbbVie and Genentech expect to move the compound into
later-stage clinical trials in the near future.

About Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia is the second most common leukemia in adults,
affecting approximately 124,000 people in the European Union. 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 includes a diverse group of blood cancers that
originates in lymphocytes, a type of white blood cell that is part of the
body's immune system. NHL is the most common hematological cancer and the
fifth leading cause of cancer death. In the EU, NHL affects approximately
90,000 to 138,000 people.

Mantle cell lymphoma is an aggressive, rapidly progressive subtype of NHL. 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 www.abbvie.com.Follow @abbvie on Twitter or view careers on our
Facebookor LinkedIn page.

SOURCE AbbVie

Website: http://www.abbvie.com
Contact: Media, David Freundel, +1-847-937-4522, or Investors, Liz Shea,
+1-847-935-2211
 
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