AbbVie Provides Update on VENCLEXTA®/VENCLYXTO® (venetoclax) Multiple Myeloma Program
NORTH CHICAGO, Ill., March 19, 2019 /PRNewswire/ -- AbbVie(NYSE: ABBV), a research-based global biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on all clinical trials evaluating venetoclax (VENCLEXTA®/VENCLYXTO®) for the investigational treatment of multiple myeloma. The partial clinical hold follows a review of data from the ongoing Phase 3 BELLINI trial (M14-031), a study in relapsed/refractory multiple myeloma, in which a higher proportion of deaths was observed in the venetoclax arm compared to the control arm of the trial. As a result of this action, no new patients should be enrolled in any studies of venetoclax for multiple myeloma until a further analysis of the data is completed. Patients who are currently enrolled in studies and receiving benefit from the therapy may continue with treatment, after consultation with their physician.
This action does not impact any of the approved indications for venetoclax, such as chronic lymphocytic leukemia (CLL) or acute myeloid leukemia (AML), and is limited to investigational clinical trials in multiple myeloma. AbbVie remains confident in the benefit/risk profile of venetoclax in those approved indications.
"We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial. We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the multiple myeloma program," said Michael Severino, M.D., vice chairman and president, AbbVie. "We will continue to further the research and development of venetoclax and other therapies with the potential to transform the standards of care in blood cancers."
AbbVie has informed clinical trial investigators involved in the studies evaluating venetoclax for the treatment of multiple myeloma of the results and will work with them to proceed as appropriate and in the best interest of each patient who may be receiving benefit from venetoclax and who elects to continue receiving treatment. Additional analyses are ongoing, and data will be published in a peer-reviewed journal and/or presented at a future medical meeting.
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.
BELLINI is a multicenter, randomized, double blind study of bortezomib and dexamethasone in combination with either venetoclax or placebo in patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy and are sensitive or naïve to proteasome inhibitors.1 The BELLINI study met its primary endpoint of progression-free survival (22.4 months vs. 11.5 months, hazard ratio [HR] 0.63, 95% confidence interval [CI]: 0.44-0.90) and demonstrated statistically significant improvements in overall response rate (82% vs. 68%) and very good partial response or better (59% vs. 36%) in the venetoclax arm compared to the control arm.
Patients should talk to their doctor immediately if they are receiving venetoclax for the treatment of multiple myeloma. For medical-related questions, please call: 1-800-633-9110.
The details of the FDA review of the Phase 3 BELLINI study included the following safety updates:
Patients deriving benefit in all ongoing trials evaluating venetoclax in multiple myeloma can continue treatment, in agreement between the individual patient and physician.
About VENCLEXTA®/VENCLYXTO® (venetoclax)
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. Venetoclax is not approved by any regulatory authority, in any country for the treatment of multiple myeloma. 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 Information2
VENCLEXTA is a prescription medicine used:
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.
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.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:
What should I avoid while taking VENCLEXTA?
What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
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.
Important VENCLYXTO® (venetoclax) EU Safety Information3
VENCLYXTO (venetoclax) Indication
Venclyxto in combination with rituximab is indicated for the treatment of adult patients with chronic lymphocytic leukaemia(CLL) who have received at least one prior therapy.
Venclyxto monotherapy is indicated for the treatment of CLL:
Special Warnings & Precautions for Use
Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.
Live vaccines should not be administered during treatment or thereafter until B-cell recovery.
Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.
CYP3A4 inducers may decrease VENCLYXTO plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.
The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with rituximab or as monotherapy were pneumonia, febrile neutropenia and TLS.
Discontinuation due to adverse reactions occurred in 16% of patients receiving venetoclax plus rituximab and 9% receiving venetoclax monotherapy. Dosage adjustments due to adverse reactions occurred in 15% of patients receiving venetoclax plus rituximab and 2% receiving venetoclax monotherapy. Dose interruptions occurred in 71% of patients treated with the combination of venetoclax and rituximab.
VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.
This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Oncology
1 Clinicaltrials.gov (2018). NCT02755597: A study evaluating venetoclax (ABT-199) in multiple myeloma subjects who are receiving bortezomib and dexamethasone as standard therapy. Accessed March 2019.
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