AbbVie announced on July 28, 2016, the initiation of a Phase 3 clinical trial to study the safety and efficacy of venetoclax in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and have received one to three prior lines of therapy. The combination of venetoclax, bortezomib and dexamethasone will be compared to treatment with bortezomib, dexamethasone and placebo.(1) Bortezomib, a proteasome inhibitor, and dexamethasone, a corticosteroid, are both common therapies used to treat symptomatic multiple myeloma.(3)
Venetoclax is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and by AbbVie outside of the U.S.
“We have a comprehensive development strategy for venetoclax, with several ongoing clinical trials across a range of hematologic malignancies and multiple lines of therapy as a single agent and in combination with other medicines,” said Michael Severino, M.D., executive vice president, Research and Development and chief scientific officer, AbbVie. “This Phase 3 trial represents our commitment to identifying the full potential of this therapy through our clinical development program and is an important step in our goal to provide a possible treatment for multiple myeloma patients.”
The randomized, double-blind, placebo-controlled, Phase 3 clinical trial aims to recruit approximately 240 patients. The primary efficacy endpoint of the trial is progression-free survival (PFS). Secondary pre-specified outcome measures include overall survival (OS), objective response rate (ORR) and duration of response (DoR), as well as other efficacy and safety outcome measures.1 More information on the Phase 3 trial is available at www.clinicaltrials.gov (NCT02755597).
Multiple myeloma is the second most common blood cancer and begins in plasma cells in the bone marrow. When plasma cells in the marrow become cancerous, they can grow uncontrollably and produce abnormal proteins (m proteins) which can cause tumors, typically developing in the bone. When a patient has multiple plasma cell tumors, they have multiple myeloma.(2)
About VENCLEXTA™ (venetoclax) in the U.S.
Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor currently approved as VENCLEXTA™ (venetoclax) tablets in the U.S. and indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.4 The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.(4)
The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells. VENCLEXTA was designed to selectively inhibit the BCL-2 protein.(4)
VENCLEXTA is being developed by AbbVie and Genentech, a member of the Roche Group. Together, the companies are committed to BCL-2 research with VENCLEXTA, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with early phase studies in several cancers. VENCLEXTA is under evaluation by Health Authorities in multiple countries, and not approved for markets outside of the U.S. AbbVie is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.
The full prescribing information for VENCLEXTA can be found here.
1 Clinicaltrials.gov. NCT02755597. A study evaluating venetoclax (ABT-199) in multiple myeloma subjects who are receiving bortezomib and dexamethasone as standard therapy. [ONLINE] Available at: https://clinicaltrials.gov/ct2/show/NCT02755597?term=NCT02755597&rank=1. Accessed July 2016.
2 Multiple Myeloma Research Foundation. Learn the basics about multiple myeloma. https://www.themmrf.org/multiple-myeloma/. Accessed July 2016.
3 Moreau, P., Attal, M. and Facon, T. (2015). Frontline therapy of multiple myeloma. Blood, 125, pp. 3076-3084. [ONLINE] Available at: http://www.bloodjournal.org/content/125/20/3076.long?sso-checked=true. Accessed July 2016.
4 VENCLEXTA [Package Insert]. North Chicago, Ill.: AbbVie Inc.
Patient Assistance Program
For those who qualify, AbbVie and Genentech offer patient assistance programs for people taking VENCLEXTA in the U.S.
U.S. 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 doctor will do tests for TLS. It is important to keep your appointments for blood tests. 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. Tell your doctor 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.
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.
Tell your doctor 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 doctor
What should I tell my doctor before taking VENCLEXTA?
Before taking VENCLEXTA, tell your doctor 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 doctor tells you it is okay
Are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your doctor 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
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 count (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your doctor will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your doctor right away if you have a fever or any signs of an infection