AbbVie to Present New Data from Several Investigational Studies of Venetoclax as Monotherapy or in Combination for the Management of a Number of Difficult-to-Treat Blood Cancers at 23rd European Hematology Association (EHA) Annual Congress

NORTH CHICAGO, Ill., May 31, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced it will present data from clinical trials across multiple blood cancers evaluating venetoclax, a first-in-class oral B-cell lymphoma-2 (BCL-2) inhibitor, as monotherapy and in combination with other therapies at the 23^rd European Hematology Association (EHA) Annual Congress, June 14-17, in Stockholm, Sweden. A total of 11 abstracts will be presented, including results of venetoclax in chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

Studies of venetoclax in CLL and AML have been chosen for oral presentations, including an undetectable minimal residual disease (uMRD) sub-analysis from the pivotal Phase 3 MURANO study of venetoclax in combination with rituximab in patients with relapsed/refractory (R/R) CLL. Minimal residual disease is an objective measure of disease defined by the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.¹ Prospective clinical trials have suggested that achieving undetectable minimal residual disease, also known as MRD negativity (MRD-), may have a prognostic impact on clinical outcomes.²

"The breadth of venetoclax studies being presented at the European Hematology Association Annual Congress, across four blood cancers, is an indicator of the utility, versatility and potential to advance care for patients living with blood cancer around the world,"³ said Neil Gallagher, M.D., Ph.D., head of oncology clinical development, AbbVie. "As a company, we are committed to exploring additional therapeutic applications for venetoclax in our efforts to address major unmet medical needs, and develop novel treatments that work against key pathways of disease progression."

Key presentations featuring venetoclax include:

Venetoclax in CLL

• High, Durable Minimal Residual Disease Negativity (MRD-) with Venetoclax + Rituximab (VenR) in Relapsed/Refractory (R/R) CLL: MRD Kinetics from Phase 3 MURANO Study. Hillmen et al.; Abstract S805; Oral Presentation; Saturday, June 16, 2018, 11:45 a.m.-12:00 p.m. CEST
• Durability Response to Venetoclax (VEN) in Patients with CLL Who Are Relapsed/Refractory after Ibrutinib and/or Idelalisib. Byrd et al.; Abstract PF340; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
• Impact of TP53 Mutated Clone Size on Outcome of Relapsed/Refractory (R/R) CLL Patients Treated with Venetoclax plus Rituximab within the Phase 3 MURANO Study. Kater et al.; Abstract PF344; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
• Venetoclax Improves Quality of Life for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Cochrane et al.; Abstract PS1438; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST
• Indirect Treatment Comparison of Venetoclax Plus Rituximab with B-Cell Receptor Inhibitors in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Mato et al.; Abstract PF358; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
• Management, Adverse Events, and Outcomes of 282 CLL Patients Treated with Venetoclax in the Real World. Nabhan et al.; Abstract PF342; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST

Venetoclax in AML

• Durable Response with Venetoclax in Combination with Decitabine or Azacitadine in Elderly Patients with Acute Myeloid Leukemia (AML). DiNardo et al.; Abstract S1563; Oral Presentation; Sunday, June 17, 2018; 8:45-9:00 a.m. CEST
• Cytogenic and Molecular Drivers of Outcome with Venetoclax-Based Combination Therapies in Treatment-Naïve Elderly Patients with AML. Strickland et al.; Abstract PS982; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST

Venetoclax in MM

• Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Costa et al.; Abstract PF558; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
• Venetoclax Monotherapy and Combined with Dexamethasone as Targeted Therapy for Relapsed/Refractory t(11;14) Multiple Myeloma. Kaufman et al.; Abstract PS1317; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST

Venetoclax in ALL

• Venetoclax and Navitoclax with Chemotherapy is Efficacious in Patients with Relapsed Acute Lymphoblastic Leukemia. Alexander et al.; Abstract PS928; Poster Session, Saturday, June 16, 2018; 5:30-7:00 p.m. CEST

The EHA 2018 Annual Congress abstracts are available at www.ehaweb.org.

About VENCLYXTO^® (venetoclax) 
VENCLYXTO^® (venetoclax), an oral B-cell lymphoma-2 (BCL-2) inhibitor, is indicated for the treatment of chronic lymphocytic leukemia (CLL) in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.⁴ It is also being evaluated for the treatment of patients with various blood cancer types.^4,5,6,7,8 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.⁴ VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.⁴

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. 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 studies in several other cancers.

Venetoclax is currently approved in the European Union, Switzerland, Argentina, Australia, Mexico, Puerto Rico, Israel, USA, and Canada. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.

For more information on AbbVie's research in oncology, please read, "Breaking the Rules of Science to Treat Cancer," on www.abbvie.com.

Important Venclyxto (venetoclax) EU Safety Information

Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John's wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use 
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS.  Blood chemistries should be monitored and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. 

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. 

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.

Avoid coadministration with strong or moderate CYP3A inducers.  These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphatemia, vomiting and constipation.

The most frequently occurring adverse reactions (>=2%) were pneumonia, febrile neutropenia and TLS. 

Discontinuations due to adverse reactions occurred in 9.1% of patients and dosage adjustments due to adverse reactions occurred in 11.8% of patients.

Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS.  Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.

This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie's oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 200 clinical trials and more than 20 different tumor types. For more information, please visit http://abbvieoncology.com.

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

Forward-Looking Statements
Some statements in this news release are, or may be considered, 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," of AbbVie's 2017 Annual Report on Form 10-K, which has 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 Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;806398.
² Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl 5):v78-v84.
³ World Cancer Research Fund International. Worldwide data. Available at: http://www.wcrf.org/int/cancer-facts-figures/worldwide-data Last accessed May 17, 2018.
⁴ Summary of Product Characteristics for VENCLYXTO.
⁵ Clinicaltrials.gov. NCT01889186: A Study of the Efficacy of ABT-199 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia with the 17p Deletion. Accessed May 2018.
⁶ Clinicaltrials.gov. NCT01994837: A Phase 2 Study of ABT-199 in Subjects with Acute Myelogenous Leukemia (AML). Accessed May 2018.
⁷ Clinicaltrials.gov. NCT01794520: Study Evaluating ABT-199 in Subjects with Relapsed or Refractory Multiple Myeloma. Accessed May 2018.
⁸ Clinicaltrials.gov. NCT01328626: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma. Accessed May 2018.

SOURCE AbbVie

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