News

NORTH CHICAGO, Ill., Nov. 5, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a leading biopharmaceutical company, will present data from clinical trials evaluating the company's oncology portfolio during the 57^th American Society of Hematology Annual Meeting (ASH), December 5-8, in Orlando, Fla. Notably, data scheduled for presentation include results from studies of venetoclax, an investigational oral B-cell lymphoma-2 (BCL-2) inhibitor, in chronic lymphocytic leukemia (CLL) and other hematological malignancies.

Additionally, researchers will present data from studies of ibrutinib (IMBRUVICA®), an inhibitor of Bruton's tyrosine kinase (BTK), as a single-agent and in combination with other therapies in several hematologic malignancies, including CLL, mantle cell lymphoma (MCL), follicular lymphoma (FL), multiple myeloma (MM) and diffuse large B-cell Lymphoma (DLBCL).

"The breadth and depth of the data we are presenting at ASH underscore our commitment to developing treatment options for people affected by blood cancers," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "We have made significant progress in advancing our deep and robust pipeline and are excited to share the results of some of our key clinical trials."

Meeting abstracts are available at http://www.hematology.org/Annual-Meeting/Abstracts/.  

Select presentations of clinical studies evaluating medicines in AbbVie's oncology pipeline and portfolio include:

Venetoclax

• Venetoclax (ABT-199 / GDC-0199) Monotherapy in Patients with CLL Refractory to or Relapsed Following Ibrutinib or Idelalisib Therapy; J. Jones et al.; Abstract 715; Oral Session; Monday, December 7, 2015; 2:45-4:15 p.m. EST
• Deep and Durable Response Following Venetoclax (ABT-199 / GDC-0199) Combined with Rituximab in Patients with Relapsed/Refractory CLL; S. Ma, et al.; Abstract 830; Oral Session; Monday, December 7, 2015; 4:30-6 p.m. EST
• Results of the Safety Run-in Phase of CLL14: Obinutuzumab and Venetoclax (GDC0199/ ABT199) with Obinutuzumab and Chlorambucil in Patients with Previously Untreated CLL and Coexisting Medical Conditions; K. Fischer; Abstract 496; Oral Session; Monday, December 7, 2015; 7-8:30 a.m. EST
• Venetoclax (GDC-0199/ABT-199) and Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated CLL– Results from a Phase 1b Study; I. Flinn et al.; Abstract 494; Oral Session; Monday, December 7, 2015; 7-8:30 a.m. EST
• A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in Combination with Decitabine or Azacitidine in Treatment-Naive Patients with AML; C. DiNardo et al.; Abstract 327; Oral Session; Sunday, December 6, 2015; 4:30-6 p.m. EST

IMBRUVICA

• Results from the International, Randomized Phase 3 Study of Ibrutinib Versus Chlorambucil in Patients 65 Years and Older with Treatment-Naive CLL/SLL (RESONATE-2TM); A. Tedeschi et al; Abstract 495; Oral Session; Monday, December 7, 2015; 7:30 a.m. ET 
• Ibrutinib Plus Bendamustine/Rituximab (BR) is Associated with Greater Reductions in Fatigue than Placebo Plus BR Among Fatigued Chronic Lymphocytic Leukemia Patients Who Are Candidates for Chemotherapy; F. Traina et al.; Abstract 267; Oral Session; Sunday, December 6, 2015; 12:30 p.m. ET  
• Combination Treatment with the Bruton's Tyrosine Kinase Inhibitor Ibrutinib and Carfilzomib in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma: Initial Results from a Multicenter Phase 1/2b Study; A. Chari et al.; Abstract 377; Oral Session; Sunday, December 6, 2015; 5:30 p.m. ET 
• Ibrutinib vs Temsirolimus: Results From a Phase 3, International, Randomized, Open-Label, Multicenter Study in Patients With Previously Treated Mantle Cell Lymphoma (MCL); S. Rule et al.; Abstract 469; Oral Session; Monday, December 7, 2015; 7:00 a.m. ET 
• Ibrutinib Plus Rituximab in Treatment-Naïve Patients with Follicular Lymphoma: Results from a Multicenter, Phase 2 Study; N. Fowler et al.; Abstract 470; Oral Session; Monday, December 7, 2015; 7:15 a.m. ET
• Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma (Alliance 051103); C. Ujjani et al.; Abstract 471; Oral Session; Monday, December 7, 2015; 7:30 a.m. ET 
• Phase I Study of Dose-Adjusted-TEDDI-R with Ibrutinib in Untreated and Relapsed/Refractory Primary CNS Lymphoma; K. Dunleavy et al.; Abstract 472; Oral Session; Monday, December 7, 2015; 7:45 a.m. ET 
• Outcome of Ibrutinib Treatment by Baseline Genetic Features in Patients with Relapsed or Refractory CLL/SLL With del17p in the RESONATE-17 Study; S. Stilgenbauer; Abstract 833; Oral Session; Monday, December 7, 2015; 5:30 p.m. ET 
• Ibrutinib Responsive MicroRNAs and Upregulation of Tumor Suppressor Targets in Chronic Lymphocytic Leukemia; A. Saleh at al.; Abstract 487; Oral Session; Monday, December 7, 2015; 7 a.m. ET 
• High Sensitivity Testing Show Multiclonal Mutations in Patients with CLL Treated with BTK Inhibitor and Lack of Mutations in Ibrutinib-Naïve Patients; M. Albitar et al.; Abstract 716; Oral Session; Monday, December 7, 2015; 3 p.m. ET 
• The Role of PIM1 in the Ibrutinib-Resistant ABC Subtype of Diffuse Large B-Cell Lymphoma; X. Kuo et al.; Abstract 699; Oral Session; Monday, December 7, 2015; 3:15 p.m. ET

Duvelisib

• Preliminary Results of a Phase Ib Study of Duvelisib in Combination with FCR (dFCR) in Previously Untreated, Younger Patients with CLL; M. Davids et al.; Abstract 4158; Poster Session; Monday, December 7, 2015; 6-8 p.m. EST
• Combination Trial of Duvelisib (IPI-145) with Bendamustine, Rituximab, or Bendamustine/Rituximab in Patients with Lymphoma or Chronic Lymphocytic Leukemia; I. Flinn, et al.; Abstract 3928; Poster Session; Monday, December 7, 2015; 6:00-8:00 p.m. EST
• Dual Inhibition of PI3K-Delta and Gamma By Duvelisib (IPI-145) Impairs CLL B- and T-Cell Migration, Survival and Proliferation in a Murine Xenograft Model Using Primary Chronic Lymphocytic Leukemia Cells; S. Chen et al.; Abstract 1753; Poster Session; Saturday, December 5, 2015; 5:30-7:30 p.m. EST

Empliciti (Elotuzumab)

• Effects of Elotuzumab on Soluble SLAMF7 Levels in Multiple Myeloma; J. Postelnek et al.; Abstract 2964; Poster Session; Sunday, December 6, 2015; 6-8 p.m. EST
• ELOQUENT-2 Update: A Phase 3, Randomized, Open-Label Study of Elotuzumab in Combination with Lenalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma – 3-Year Follow-up, M. Dimopoulos et al.; Abstract 28; Oral Session; Saturday, December 5, 2015; 7:30-9 a.m. EST
• Elotuzumab Plus Bortezomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma; 24-Month Follow-up; A. Palumbo et al.; Abstract 510; Oral Session; Monday, December 7, 2015; 7-9:30 a.m. EST
• An Ongoing Multinational Observational Study in Multiple Myeloma (PREAMBLE): Preliminary Report on Patient Survival; G. Cook et al.; Abstract 2093; Poster Session; Saturday, December 5, 2015; 5:30-7:30 p.m. EST

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 (programmed cell death) of some cells, including lymphocytes, and can be over expressed 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 earlier phase 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 Elotuzumab
Elotuzumab is an investigational immunostimulatory antibody targeted against Signaling Lymphocyte Activation Molecule Family 7 (SLAMF7), a cell-surface glycoprotein that is highly expressed on multiple myeloma cells and Natural Killer (NK) cells, but is not detected on normal solid tissue cells. Elotuzumab is being investigated to determine whether through both direct activation and engagement of NK cells, the compound may target and kill SLAMF7 expressing myeloma cells. In 2014, the U.S. FDA granted elotuzumab Breakthrough Therapy Designation for use in combination with one of the chemotherapy treatments for multiple myeloma (lenalidomide, used in combination with dexamethasone) in patients who have received one to three prior treatments. Elotuzumab is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority. AbbVie and Bristol-Myers Squibb are co-developing elotuzumab, with Bristol-Myers Squibb leading the commercialization of the agent.

About Duvelisib
Duvelisib is an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, two proteins that are known to help support the growth and survival of malignant B-cells. PI3K-delta signaling can lead to the proliferation of malignant B-cells, and both PI3K-gamma and PI3K delta play a role in the formation and maintenance of the supportive tumor microenvironment. AbbVie and Infinity Pharmaceuticals, Inc. are jointly developing duvelisib in various cancer types.

Duvelisib is being evaluated in several studies, including a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma, a Phase 3 study in patients with previously treated follicular lymphoma and a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia. Duvelisib is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

About IMBRUVICA
IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients (including treatment-naive) who have del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost, and all patients (including treatment-naive) with Waldenström's macroglobulinemia. IMBRUVICA is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.¹

IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton's tyrosine kinase (BTK).1 IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway, and is currently the only product to have received three Breakthrough Therapy Designations.

BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.^1,2 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.¹

IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers. More than 6,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 13 Phase III trials have been initiated with IMBRUVICA and 67 trials are registered on www.clinicaltrials.gov.

To learn more about the medical terminology used in this news release, please visit http://stedmansonline.com/.

INDICATIONS 
IMBRUVICA is indicated in the US to treat people with:

• Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
• Chronic lymphocytic leukemia (CLL) with 17p deletion
• Waldenstrom's macroglobulinemia
• Mantle cell lymphoma (MCL) who have received at least one prior therapy – accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

Patients taking IMBRUVICA for CLL or WM should take 420 mg taken orally once daily (or three 140 mg capsules once daily).

Patients taking IMBRUVICA for MCL should take 560 mg taken orally once daily (or four 140 mg capsules once daily).

Capsules should be taken orally with a glass of water. Capsules should be taken whole. Do not open, break, split or chew the capsules.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS FOR U.S. PRESCRIBERS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA^®. Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA^®. The mechanism for the bleeding events is not well understood. IMBRUVICA^® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA^® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal infections have occurred with IMBRUVICA^® therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA^®. Monitor patients for fever and infections and evaluate promptly.

Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated with IMBRUVICA^®. Monitor complete blood counts monthly.

Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA^®, particularly in patients with cardiac risk factors, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. If atrial fibrillation persists, consider the risks and benefits of IMBRUVICA^® treatment and dose modification.

Second Primary Malignancies - Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA^®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome - Tumor lysis syndrome has been reported with IMBRUVICA^® therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g., high tumor burden).

Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA^® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA^®. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS
The most common adverse reactions (≥25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 52%, 43%), neutropenia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%), anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), musculoskeletal pain (37%, 28%**, NA***), bruising (30%, 12%**, 16%**), nausea (31%, 26%, 21%), upper respiratory tract infection (34%, 16%, 19%), and rash (25%, 24%**, 22%**).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

**Includes multiple ADR terms.

***Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematological adverse reactions (> 5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse events.

Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse events. Most frequent adverse events leading to discontinuation were infections, subdural hematomas, and diarrhea in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors - Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA^® dose.

CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA^® dose.

Please see Full Prescribing Information for U.S. Prescribers: http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

About Pharmacyclics, An AbbVie Company
Pharmacyclics, a wholly-owned subsidiary of AbbVie (NYSE: ABBV), is focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune-mediated diseases. Pharmacyclics' mission is to develop and commercialize novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medical needs. 

Pharmacyclics markets IMBRUVICA and has three product candidates in clinical development and several preclinical molecules in lead optimization. Pharmacyclics is committed to high standards of ethics, scientific rigor and operational efficiency as it moves each of these programs toward commercialization. To learn more, please visit www.pharmacyclics.com.

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 and AbbVie's oncology portfolio, 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, 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 and in item 1A, "Risk Factors" of Part II of AbbVie's second quarter 2015 Quarterly Report on Form 10-Q, which have 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 IMBRUVICA Prescribing Information, January 2015 
² Genetics Home Reference. Isolated growth hormone deficiency. Available at: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed June 2015. 

SOURCE AbbVie