AbbVie (NYSE:ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) granted a fifth Breakthrough Therapy Designation (BTD) to venetoclax, for use in combination with obinutuzumab as a fixed duration investigational combination, for untreated adult patients with chronic lymphocytic leukemia (CLL). According to the FDA, this designation is intended to expedite the review of therapies for serious or life-threatening conditions. The designation coincides with the completion of the supplemental New Drug Application (sNDA) submission to the FDA for approval in previously-untreated CLL patients.
The FDA will review the venetoclax and obinutuzumab combination under its Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective cancer medicines are available to patients as early as possible.
“We studied the venetoclax and obinutuzumab combination with a fixed treatment duration and found these medicines, used together, may enable some CLL patients to live longer without their disease getting worse, leading to longer progression-free survival, while remaining off therapy,” said Mohamed Zaki, M.D., Ph.D., vice president, global head of hematology development, AbbVie. “Under the RTOR program, we are determined to work with the FDA and bring this first- and only-in-class medicine to previously-untreated CLL patients earlier than expected.”
The sNDA for the venetoclax and obinutuzumab combination is based on data from the Phase 3 CLL14 trial, which studied patients receiving the combination treatment for 12 months as their first treatment for CLL. CLL14 is the first randomized trial in CLL to examine a chemotherapy-free, fixed duration treatment regimen.
The FDA’s standard review time for drug applications is six to 10 months.1 The RTOR program focuses on the early submission of data most relevant to assessing the product’s safety and effectiveness. RTOR allows the FDA to review much of the data before it is formally submitted to the FDA.
VENCLEXTA® (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 Chronic Lymphocytic LeukemiaCLL is typically a slow-progressing cancer of the bone marrow and blood in which types of white blood cells called B lymphocytes become cancerous and multiply abnormally.2 In the U.S., CLL accounts for more than 20,000 newly diagnosed cases of leukemia each year.2
About the Phase 3 CLL14 TrialThe prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of venetoclax and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in previously-untreated patients with CLL and coexisting medical conditions. The therapies were administered for a fixed duration of 12 months for venetoclax in combination with six cycles of obinutuzumab. The trial enrolled 445 patients, all of whom were previously-untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. The primary endpoint was progression-free survival (PFS) based on investigator assessment, using iwCLL criteria.3
Key secondary endpoints were PFS as assessed by an independent review committee, minimal residual disease (MRD)-negativity in peripheral blood and bone marrow, overall and complete response rates, MRD-negativity in complete response in peripheral blood and bone marrow, and overall survival.
About VENCLEXTA® (venetoclax tablets) (US) VENCLEXTA® 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.4
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.
The efficacy and safety of venetoclax in patients with previously-untreated CLL has not been evaluated by the U.S. Food and Drug Administration, the European Medicines Agency or any health authority.
In April 2016, the U.S. FDA first granted accelerated approval of VENCLEXTA for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.5 The FDA approved this indication under accelerated approval based on overall response rate.5 Based on the results of the MURANO study, VENCLEXTA was approved in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.4 In November 2018, VENCLEXTA was approved 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.6
Venetoclax 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 Safety Information (US)
VENCLEXTA is a prescription medicine used:
— to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior treatment.
— 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 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 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 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. 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 rituximab in people with CLL include low white blood cell counts, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.
The most common side effects of VENCLEXTA when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling of your arms, legs, hands, and feet; and cough.
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.pparx.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. 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://www.abbvie.com/oncology.
About AbbVieAbbVie 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 StatementsSome 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 U.S. Food and Drug Administration (2018). “Real-Time Review of Drug Applications is Now a Reality.” September 20, 2018 issue.2 American Cancer Society (2018). Chronic Lymphocytic Leukemia (CLL). http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf. Accessed January 2019.3 Clinicaltrials.gov (2018). NCT02242942: A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax (GDC-0199) Versus Obinutuzumab + Chlorambucil in Participants With Chronic Lymphocytic Leukemia. https://clinicaltrials.gov/ct2/show/NCT02242942. Accessed February 2019.4 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, Ill.: AbbVie Inc.5 U.S. Food and Drug Administration (2016). News and Events: FDA approves new drug for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm495253.htm. Accessed January 2019.6 U.S. Food and Drug Administration (2018). Approved Drugs: FDA approves venetoclax in combination for AML in adults. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626499.htm. Accessed January 2019.
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