NORTH CHICAGO, Ill.,?Oct. 16, 2020?/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has provided full approval to VENCLEXTA? (venetoclax) in combination with?azacitidine, or decitabine,?or low-dose cytarabine (LDAC) for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy. The?approval is supported by data from the Phase 3 VIALE-A?(M15-656)?and VIALE-C (M16-043)?studies and updated data from the Phase?1b?M14-358 and the Phase 1/2 M14-387 studies. The FDA previously granted accelerated approval to VENCLEXTA for this indication in 2018.⁵ "AML is a complex and challenging disease with generally low survival rates. This approval is significant because data from our VIALE-A trial has shown that newly-diagnosed patients, who cannot undergo intensive chemotherapy, lived longer when treated with VENCLEXTA plus azacitidine than those treated with azacitidine alone," said?Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development, AbbVie. "This trial also provides physicians more information for managing patients - from treatment initiation, to assessing response and management post disease remission." Positive overall survival (OS) data seen at an interim analysis of the VIALE-A trial led to an early submission supporting the FDA approval of VENCLEXTA in AML. The trial showed patients on the active regimen of VENCLEXTA plus azacitidine achieved a 34% reduction in the risk of death compared to azacitidine in combination with placebo?(Hazard Ratio [HR]=0.66 [95% CI: 0.52-0.85], p<0.001).?The median OS for patients in the VENCLEXTA arm was 14.7 months (95% CI: 11.9, 18.7) versus 9.6 months in the placebo arm (95% CI: 7.4, 12.7). Additionally, patients in the VENCLEXTA?plus azacitidine arm achieved a complete remission (CR) rate of 37% (95% CI: 31%, 43%) with a median duration of CR of 18.0 months (95% CI: 15.3, -) compared with?patients in the placebo plus azacitidine arm with a CR rate of 18% (95% CI: 12%, 25%) with a median duration of CR of 13.4 months (95% CI: 8.7, 17.6). The observed safety profile was generally consistent with the known safety profile of VENCLEXTA in combination with azacitidine. For patients taking VENCLEXTA in combination with azacitidine, the most frequent serious adverse reactions (ARs; =5%) at first use were febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%) and hemorrhage (6%).^1,6 Data from VIALE-A was presented for the first time as a late-breaking abstract at the 25^th?European Hematology Association (EHA) Annual Congress in?June 2020?and recently published in the?New England Journal of Medicine.⁷ "For far too long, people with AML had very few treatment options, aside from very intense chemotherapy. Today's news continues the progress of bringing more treatment options to patients with this devastating disease," said?Lee Greenberger, Ph.D., chief scientific officer of The Leukemia & Lymphoma Society. Data from the VIALE-C trial was presented at both the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting and the EHA Annual Congress and previously published in?Blood.⁸?The median OS for VENCLEXTA in combination with LDAC was 7.2 months (95% CI: 5.6, 10.1) and 4.1 months for LDAC in combination with placebo (95% CI: 3.1, 8.8). The HR for the primary endpoint of OS was 0.75 (95% CI: 0.52-1.07; p=0.114). The trial did not meet its primary endpoint of statistically significant improvement of OS for patients with AML who are ineligible for intensive chemotherapy at the time of the planned analysis. Efficacy was based on the rate of CR and duration of CR with supportive evidence of rate of CR + complete remission with partial hematologic recovery (CR+CRh), duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. In the VENCLEXTA arm, the most frequent serious ARs were (=10%) pneumonia (17%), febrile neutropenia (16%) and sepsis (excluding fungal; 12%).^1,9 AML is an aggressive and difficult-to-treat blood cancer with a low survival rate.^2,3?Despite recent advances in available therapies, the five-year survival rate for patients diagnosed with AML remains approximately 29%.¹⁰?AML typically worsens quickly, and due to age or comorbidities, not all patients are eligible to receive intensive chemotherapy.¹¹ The FDA reviewed the clinical data under the FDA's Real-Time Oncology Review (RTOR) pilot program and Project Orbis initiative, which led to approval in the U.S. in?October 2020. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The U.S. FDA, the Australian Therapeutic Goods Administration, Swissmedic, Health Canada and ANVISA (Ag?ncia Nacional de Vigil?ncia Sanit?ria) collaborated on this review based on the marketing applications submitted in their respective countries. 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. About the VIALE-A and VIALE-C Clinical Trials VIALE-A (M15-656)?Phase 3 Trial^1,7 A total of 431 patients were randomized in the double-blind, placebo-controlled, multicenter, Phase 3 VIALE-A trial, which evaluated the efficacy and safety of VENCLEXTA in combination with azacitidine (n=286) in patients with AML who are ineligible for standard induction therapy versus azacitidine in combination with placebo (n=145).?The primary endpoint was OS. The VENCLEXTA plus azacitidine?combination showed a median OS of 14.7 months (95% CI: 11.9, 18.7) versus 9.6 months (95% CI: 7.4, 12.7) with azacitidine in combination with placebo. The study also met its secondary endpoints, with the VENCLEXTA?combination arm resulting in a CR rate of 37% (95% CI: 31, 43) and a CR+CRh rate of 65% (95% CI: 59, 70) compared to a CR rate of 18% (95% CI: 12, 25) and a CR+CRh rate of 23% (95% CI: 16, 30) in the placebo arm. The median time to first response of CR or CRh was 1.0 months (range: 0.6 to 14.3 months) with VENCLEXTA?in combination with azacitidine. The median duration of treatment was 7.6 months (range: <0.1 to 30.7 months) in the VENCLEXTA arm. The most frequent ARs (=30% with a difference between arms of =5%) for patients taking VENCLEXTA in combination with azacitidine were mostly hematologic and gastrointestinal in nature and consisted of, nausea (44%), diarrhea (43%), febrile neutropenia (42%), musculoskeletal pain (36%), fatigue (31%), and vomiting (30%). Serious adverse reactions were reported in 83% of patients in the VENCLEXTA arm, with the most frequent serious ARs (=5%) being febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%) and hemorrhage (6%). VIALE-C (M16-043) Phase 3 Trial^1,9 A total of 211 patients were enrolled and treated in the randomized, double-blind, placebo-controlled, multicenter, Phase 3 VIALE-C trial, which evaluated the efficacy and safety of VENCLEXTA in combination with LDAC (n=143) versus placebo with LDAC (n=68). The primary?endpoint was OS. VENCLEXTA in combination with LDAC did not significantly improve OS versus placebo in combination with LDAC. The HR for OS was 0.75 (95% CI: 0.52, 1.07); p-value 0.114. The median OS for VENCLEXTA in combination with LDAC arm was 7.2 months (95% CI: 5.6, 10.1) and for PBO+LDAC arm was 4.1 months (95% CI: 3.1, 8.8). Efficacy was based on the rate of CR and duration of CR with supportive evidence of rate of CR+CRh, duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. The CR rate in the VENCLEXTA in combination with LDAC arm was 27% (95% CI: 20%, 35%) with a median duration of CR of 11.1 months (95% CI: 6.1, -), and the CR rate in the placebo arm was 7.4% (95% CI: 2.4%, 16%) with a median duration of CR of 8.3 months (95% CI: 3.1, - ). The CR+CRh rate in the VENCLEXTA in combination with LDAC arm was 47% (95% CI: 39%, 55%) and in the placebo arm was 15% (95% CI: 7.3%, 25%) with a median duration of CR+CRh of 11.1 months with VENCLEXTA in combination with LDAC and 6.2 months with LDAC in combination with placebo. The median time to first response of CR or CRh was 1.0 month (range: 0.7 to 5.8 months) with VENCLEXTA in combination with LDAC. The most frequent AR (=30% with a difference between arms of =5%) for patients taking VENCLEXTA in combination with LDAC was nausea (42%). Serious ARs were reported in 65% of patients in the VENCLEXTA?arm, with the most frequent (=10%) being pneumonia (17%), febrile neutropenia (16%), and sepsis (excluding fungal; 12%). About VENCLEXTA? (venetoclax)? VENCLEXTA? (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLEXTA targets the BCL-2 protein and works to help restore the process of apoptosis. VENCLEXTA 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 and to studying venetoclax in clinical trials across several blood and other cancers. VENCLEXTA is approved in more than 50 countries, including the U.S. Uses and Important VENCLEXTA??(venetoclax) U.S. Safety Information¹ Uses VENCLEXTA is a prescription medicine used:

• to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
  • are 75 years of age or older, or
    have other medical conditions that prevent the use of standard chemotherapy.

It is not known if VENCLEXTA is safe and effective in children. Important Safety Information What is the most important information I should know about VENCLEXTA? VENCLEXTA can cause serious side effects, including: Tumor lysis syndrome (TLS).?TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA. It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS.?Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased. Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects. Who should not take VENCLEXTA? Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS.

• Tell your healthcare provider about all the medicines you take,?including prescription and over-the- counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects.
• Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.

Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

• have kidney or liver problems.
• have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
• have a history of high uric acid levels in your blood or gout.
• are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
• are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for at least 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away.
• are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment and for?1 week after the last dose of VENCLEXTA.

What should I avoid while taking VENCLEXTA? You should not drink grapefruit juice or eat grapefruit,?Seville?oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood. What are the possible side effects of VENCLEXTA? VENCLEXTA can cause serious side effects, including:

• Low white blood cell counts (neutropenia).?Low white blood cell counts are common with VENCLEXTA but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA and may pause dosing.
• Infections.?Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA.

Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA. The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include?low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet. The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include?nausea, diarrhea, low platelet count, constipation, low white blood cell count, fever with low white blood cell count, tiredness, vomiting, swelling of arms, legs, hands, or feet, fever, infection in lungs, shortness of breath, bleeding, low red blood cell count, rash, stomach (abdominal) pain, infection in your blood, muscle and joint pain, dizziness, cough, sore throat, and low blood pressure. VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility. These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit?www.fda.gov/medwatch?or call 1-800-FDA-1088. If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit?AbbVie.com/myAbbVieAssist?to learn more. The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found?here.?Globally, prescribing information varies; refer to the individual country product label for complete information. About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit?http://www.abbvie.com/oncology. About AbbVie AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at?www.abbvie.com. Follow?@abbvie?on?Twitter,?Facebook,?Instagram,?YouTube?and?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, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. 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 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. 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?VENCLEXTA (venetoclax) [Package Insert].?North Chicago, IL.: AbbVie Inc. ²?D?hner H, et al. Acute myeloid leukemia.?N Engl J Med. 2015;373(12):1136-1152. ³?American Cancer Society (2019). Typical Treatment of Most Types of Acute Myeloid Leukemia (Except Acute Promyelocytic M3).?https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html. Accessed?October 2020. ⁴?Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines?) for Acute Myeloid Leukemia V.1.2021. ? National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed?October 16, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. ⁵?AbbVie (2018). AbbVie Receives US FDA Accelerated Approval for VENCLEXTA? (venetoclax) for Treatment of Newly-Diagnosed Acute Myeloid Leukemia Patients Ineligible for Intensive Chemotherapy.?https://news.abbvie.com/news/press-releases/abbvie-receives-us-fda-accelerated-approval-for-venclexta-venetoclax-for-treatment-newly-diagnosed-acute-myeloid-leukemia-patients-ineligible-for-intensive-chemotherapy.htm. Accessed?October 2020. ⁶?DiNardo CD, et al. A randomized, double-blind, placeobo-controlled study of venetoclax with azacytidine vs azacytidine in treatment-na?ve patients with acute myeloid leukemia ineligible for intensive therapy: VIALE-A. Presented at the EHA 25^th?Annual Congress. ⁷?DiNardo CD, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid. N Engl J Med. 2020;383(7):617-629. ⁸?Wei AH, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial.?https://ashpublications.org/blood/article/135/24/2137/454176/Venetoclax-plus-LDAC-for-newly-diagnosed-AML. Accessed?October 2020. ⁹?Wei AH, et al. A Phase III Study of Venetoclax Plus Low-Dose Cytarabine in Previously Untreated Older Patients with Acute Myeloid Leukemia (VIALE-C): A Six-Month Update.Presented at the 2020 ASCO Virtual Meeting. ¹⁰?National Cancer Institute (2018). Acute Myeloid Leukemia - SEER Stat Fact Sheets.?https://seer.cancer.gov/statfacts/html/amyl.html. Accessed?October 2020. ¹¹?Pettit K, Odenike O. Defining and treating older adults with acute myeloid leukemia who are ineligible for intensive therapies.?Front Oncol. 2015; 5:250.   SOURCE AbbVie