AbbVie Provides Update from Phase 3 Study Evaluating VENCLEXTA® (venetoclax) in Combination with Low-Dose Cytarabine in Newly-Diagnosed Patients with Acute Myeloid Leukemia (AML)

NORTH CHICAGO, Ill., Feb. 28, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced the VIALE-C (M16-043) trial of venetoclax (VENCLEXTA^®) in combination with low-dose cytarabine (LDAC) versus LDAC in combination with placebo did not meet its primary endpoint of statistically significant improvement of overall survival (OS) for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy at the time of the planned analysis.³

Treatment with the venetoclax combination showed a 25% reduction in the risk of death compared to LDAC with placebo (Hazard Ratio [HR]=0.75 [95% CI 0.52–1.07], p=0.11). The venetoclax with LDAC arm also showed a median OS of 7.2 months vs. 4.1 months in the LDAC arm alone. A post-hoc analysis after an additional six months of follow up showed an increase in median OS of 8.4 months in the venetoclax plus LDAC arm and 4.1 months in the placebo plus LDAC arm (HR=0.70 [95% CI 0.50-0.99]).³ Select secondary endpoints are included in the following table.

Select Secondary Endpoint Outcomes:*

The safety profile of the combination is consistent with the safety results reported in the Phase 1/2 studies that supported the U.S. Food and Drug Administration (FDA) approval of the combination. At this time, indications for venetoclax remain unchanged.

"We remain committed to AML patients and our research in AML and other blood cancers," said Neil Gallagher, M.D., Ph.D., chief medical officer and vice president of development, AbbVie. "The study results, while not statistically significant, are indicative of the clinical activity of venetoclax in combination with low-dose cytarabine."

The VIALE-C study evaluated venetoclax in combination with LDAC compared with LDAC alone in newly-diagnosed patients with AML who are ineligible for intensive chemotherapy. The median follow-up time at the end of the planned primary analysis for both arms of the trial was 12 months. Select secondary endpoints that were evaluated in the primary analysis included remission rates, transfusion independence, and event-free survival.

Consistent with prior studies in AML, the most frequently reported AEs, irrespective of cause, were hematologic and are represented in the following table.

Serious and Non-Serious Adverse Events

AML is one of the most difficult-to-treat blood cancers. It forms in the bone marrow and results in increasing numbers of abnormal white blood cells in the bloodstream and bone marrow.⁴ AML typically worsens quickly and not all patients are eligible to receive intensive chemotherapy. Age and comorbidities are common factors limiting intensive therapy.⁵ Only approximately 28 percent of patients survive five years or more.⁶

In November 2018, AbbVie received accelerated approval for VENCLEXTA in the U.S. in combination with azacitidine, decitabine, or 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 based on Phase 1/2 studies. Continued approval for this indication may be contingent upon verification and description of clinical benefit in an ongoing trial. Approval was also granted in Mexico, Israel, Puerto Rico, Peru, Brazil, Russia, Argentina, Guatemala, Uruguay, Lebanon, Bahrain, Kazakhstan, Panama, Saudi Arabia, Taiwan, Australia, and United Arab Emirates. AbbVie has provided the results from VIALE-C to the FDA and other global health authorities and will continue to work with them to ensure that venetoclax remains an appropriately managed option for patients with AML.

AbbVie has a robust AML clinical research program and is continuing to explore the potential of venetoclax and other investigational medicines in AML with several studies, including VIALE-A, a Phase 3 study of venetoclax in combination with azacitidine compared to azacitidine plus placebo in newly-diagnosed patients who are ineligible for intensive chemotherapy.

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.

About the VIALE-C (M16-043) Phase 3 Trial
A total of 211 treatment-naïve AML patients were enrolled and 210 were treated in the randomized, double-blind, placebo-controlled Phase 3 VIALE-C trial. The trial was designed to evaluate the efficacy and safety of venetoclax in combination with low dose cytarabine (LDAC) (N=143) compared with placebo in combination with LDAC (N=68). The primary efficacy endpoint was overall survival (OS) compared between the groups of patients receiving LDAC and those who received LDAC with venetoclax.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 is approved in more than 50 countries, including the U.S. AbbVie, in collaboration with Roche, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Uses and Important VENCLEXTA® (venetoclax) U.S. Safety Information⁷

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 when taking 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 health care 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 health care provider.

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

• have kidney 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 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 http://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 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, LinkedIn or Instagram.

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, competition from other products, challenges to intellectual property, 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 2018 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 Döhner H, et al. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152.
² American Cancer Society (2018). 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.
³ Clinicaltrials.gov. NCT03069352: A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy.https://clinicaltrials.gov/ct2/show/results/NCT03069352. Accessed February 28, 2020.
⁴ American Cancer Society (2018). What is Acute Myeloid Leukemia (AML)? https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html
⁵ Pettit, K and Odenike, O. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies. Front Oncol. 2015; 5:250.
⁶ National Cancer Institute (2018). Acute Myeloid Leukemia - SEER Stat Fact Sheets. https://seer.cancer.gov/statfacts/html/amyl.html.
⁷ VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.

SOURCE AbbVie

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