New England Journal of Medicine Publishes Positive Phase 3 Data of Venetoclax Combination in Acute Myeloid Leukemia (AML) Patients

• Data from Phase 3 VIALE-A study showed venetoclax plus azacitidine reduced the risk of death by 34% compared to azacitidine plus placebo in newly-diagnosed patients with AML who are ineligible for chemotherapy
• AML is one of the most aggressive blood cancers, with a very low survival rate and few options for patients who are unable to undergo intensive chemotherapy, the current standard of care(1,2)

NORTH CHICAGO, Ill., Aug. 12, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the publication of results from the Phase 3 VIALE-A clinical study in patients with AML in the New England Journal of Medicine (NEJM). The study, which evaluated newly-diagnosed AML patients who had not yet been treated and were unable to tolerate traditional intensive chemotherapy, found that venetoclax in combination with azacitidine extended overall survival (OS) compared to azacitidine plus placebo. The manuscript titled, "Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia," was published in the August 13, 2020 issue of NEJM.3

"The ability of venetoclax plus azacitidine to improve outcomes of newly-diagnosed AML patients unable to tolerate intensive chemotherapy represents a potentially practice-changing advance in AML treatment," said Courtney D. DiNardo, M.D., MSCE, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and the lead study investigator.

In the VIALE-A study, OS was the sole primary study endpoint in the U.S. OS and composite complete remission rate (CR+CRi) were co-primary endpoints in China, Japan, the European Union (EU) and EU reference countries. CR+CRi is a composite score reflecting the complete remission (CR) and CR with incomplete hematologic recovery (CRi), which is an incomplete CR with blood counts not fully recovered.4,5 Treatment with venetoclax plus azacitidine reduced the risk of death by 34% compared to azacitidine in combination with placebo (Hazard Ratio [HR]=0.66 [95% CI: 0.52-0.85], p<0.001).3 

Patients in the venetoclax combination arm had a median OS of 14.7 months (95% CI: 11.9-18.7) versus 9.6 months for patients in the placebo arm (95% CI: 7.4-12.7). Additionally, 66.4% (95% CI: 60.6-71.9) of patients treated with venetoclax plus azacitidine achieved CR+CRi versus 28.3% (95% CI: 21.1-36.3) of patients treated with azacitidine plus placebo (p<0.001). Other secondary endpoints that were published in NEJM include CR and CR with partial hematologic recovery (CR+CRh).3 

The observed safety profile in the VIALE-A trial is generally consistent with the known safety profiles of venetoclax combined with azacitidine. The most common adverse events (AEs [occurring in ≥40% of patients]) in patients receiving venetoclax plus azacitidine were mostly hematologic and gastrointestinal in nature and consisted of thrombocytopenia (46%), nausea (44%), constipation (43%), neutropenia (42%), febrile neutropenia (42%) and diarrhea (41%). The most frequent serious adverse reactions (ARs [occurring in >10% of patients]) in patients receiving venetoclax plus azacitidine were febrile neutropenia (30%) and pneumonia (17%). Tumor lysis syndrome (TLS) was reported during ramp-up in three patients in the venetoclax arm and none in the placebo arm. All were transient biochemical changes that resolved with uricosuric agents – medications that increase excretion of uric acid in the urine and decrease the concentration of uric acid in blood plasma – and calcium supplements without treatment interruption.

The VIALE-A trial results were presented as late-breaking data during the virtual 25th European Hematology Association (EHA) Annual Congress in June 2020 (abstract #LB2601).6 AbbVie, in collaboration with Genentech, submitted the results of the VIALE-A (M15-656) trial, along with data from the VIALE-C (M16-043) trial and updated data from the Phase 1/2 studies M14-358 and M14-387, to the U.S. Food and Drug Administration (FDA) to convert the accelerated approval for venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, to a full approval. AbbVie also submitted these data to additional health authorities around the world. 

AML is the most common acute leukemia in the world.7 Not all patients can tolerate standard intensive chemotherapy,8 making it among the most difficult blood cancers to treat.9 Despite advances in available therapies and care, the five-year survival rate for patients diagnosed with AML remains approximately 28%.10

Venetoclax, known by the brand name VENCLEXTA® in the U.S., 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 (M15-656) Phase 3 Trial
A total of 433 treatment-naïve, intensive chemotherapy ineligible AML patients were randomized in the double-blind, placebo-controlled Phase 3 VIALE-A trial. The trial was designed to evaluate the efficacy and safety of venetoclax in combination with azacitidine (n=286) compared with azacitidine in combination with placebo (n=145).3 

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/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 and to studying venetoclax in clinical trials across several blood and other cancers. VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S.

Uses and Important VENCLEXTA® (venetoclax) U.S. Safety Information11

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.

VENCLEXTA was approved based on response rates. Continued approval for this use may depend on the results of an ongoing study to find out how VENCLEXTA works over a longer period of time.

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 with 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.
• 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 low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of your arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.

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. For more information, ask your healthcare provider or pharmacist.

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 cannot afford your medication, contact www.medicineassistancetool.org for assistance.

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 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. AbbVie's oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 300 clinical trials and more than 20 different tumor types. 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.