NORTH CHICAGO, IL, USA I March 19, 2019 I 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.
About BELLINI
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:
- In a pre-planned analysis of the primary endpoint and ranked secondary endpoints, in the venetoclax arm 41 out of 194 (21.1%) deaths were observed, among which, 13 (6.7%) were treatment emergent (HR 2.03, 95% CI [1.042 – 3.945]). Of the 13 treatment-emergent deaths in the venetoclax arm, 8 were attributed by the investigator to an event of infection, and more than half were in the setting of refractory or progressive disease.
- In the placebo arm 11 out of 97 (11.3%) deaths were observed, among which, 1 (1.0%) was treatment emergent (occurred less than 30 days after last dose of study drug).
- The incidence of severe, grade 3-5 toxicity (86.5% vs. 87.5%, investigational vs. control arm) and serious adverse events (48.2% vs. 50.0%) was similar between the two arms. The incidence of infections (Infections and Infestation System Organ Class) was 79.8% in the investigational arm and 77.1% in the control arm. The incidence of pneumonia was 20.7% in the investigational arm and 15.6% in the placebo arm.
- Serious adverse events of infection were reported in 28.0% of patients in the investigational arm and 27.1% in the control arm. Serious adverse events of pneumonia were reported in 14.0% of patients in the investigational arm and 12.5% of patients in the placebo arm. Frequent causes of death not related to disease progression identified in the venetoclax arm were: sepsis, pneumonia, and cardiac arrest.
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® (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/VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.2
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.
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:
- in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
- in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemo immunotherapy and a B-cell receptor pathway inhibitor.
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 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.
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.
2 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
3 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.
SOURCE: AbbVie
Post Views: 21
NORTH CHICAGO, IL, USA I March 19, 2019 I 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.
About BELLINI
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:
- In a pre-planned analysis of the primary endpoint and ranked secondary endpoints, in the venetoclax arm 41 out of 194 (21.1%) deaths were observed, among which, 13 (6.7%) were treatment emergent (HR 2.03, 95% CI [1.042 – 3.945]). Of the 13 treatment-emergent deaths in the venetoclax arm, 8 were attributed by the investigator to an event of infection, and more than half were in the setting of refractory or progressive disease.
- In the placebo arm 11 out of 97 (11.3%) deaths were observed, among which, 1 (1.0%) was treatment emergent (occurred less than 30 days after last dose of study drug).
- The incidence of severe, grade 3-5 toxicity (86.5% vs. 87.5%, investigational vs. control arm) and serious adverse events (48.2% vs. 50.0%) was similar between the two arms. The incidence of infections (Infections and Infestation System Organ Class) was 79.8% in the investigational arm and 77.1% in the control arm. The incidence of pneumonia was 20.7% in the investigational arm and 15.6% in the placebo arm.
- Serious adverse events of infection were reported in 28.0% of patients in the investigational arm and 27.1% in the control arm. Serious adverse events of pneumonia were reported in 14.0% of patients in the investigational arm and 12.5% of patients in the placebo arm. Frequent causes of death not related to disease progression identified in the venetoclax arm were: sepsis, pneumonia, and cardiac arrest.
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® (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/VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.2
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.
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:
- in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
- in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemo immunotherapy and a B-cell receptor pathway inhibitor.
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 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.
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.
2 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
3 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.
SOURCE: AbbVie
Post Views: 21
