– The approval is based on the MURANO Phase 3 clinical trial, in which VENCLYXTO® plus rituximab reduced the risk of disease progression or death by 83 percent and overall survival was prolonged compared to bendamustine in combination with rituximab, a standard of care chemoimmunotherapy regimen¹
– Majority of patients (62.4 percent) treated with VENCLYXTO plus rituximab achieved high rates of undetectable minimal residual disease (also known as minimal residual disease negativity) in peripheral blood compared to 13.3 percent of patients who received bendamustine plus rituximab¹
– Today’s approval makes VENCLYXTO plus rituximab the first chemotherapy-free combination with a 24-month fixed duration for the treatment of patients with chronic lymphocytic leukemia who have received at least one prior therapy
NORTH CHICAGO, IL, USA I November 1, 2018 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, announced today that the European Commission (EC) has approved the type-II variation application for VENCLYXTO® (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy. This approval allows more patients to receive VENCLYXTO in the second-line setting and gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union (EU). The approval is valid in all 28 member states of the EU, as well as Iceland, Liechtenstein and Norway.
The EC approval is based on results from the MURANO Phase 3 randomized clinical trial, which evaluated the efficacy and safety of VENCLYXTO in combination with rituximab compared to bendamustine in combination with rituximab, an established standard of care chemoimmunotherapy regimen for patients with R/R CLL.1 At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death2) in patients who received VENCLYXTO plus rituximab, resulting in an 83 percent reduction in the risk of disease progression or death (hazard ratio [HR]:0.17; 95% confidence interval [CI]: 0.11-0.25; P<0.0001) and prolonged overall survival (OS) compared to the standard of care chemoimmunotherapy (HR: 0.48; 95% CI: 0.25-0.90; overall survival data are not yet mature).1
In the MURANO Phase 3 clinical trial, undetectable minimal residual disease (uMRD) was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,3). The majority of patients in the trial who received VENCLYXTO plus rituximab achieved uMRD in the peripheral blood, with 62.4 percent of patients achieving uMRD versus 13.3 percent with bendamustine in combination with rituximab.1 uMRD is an objective measure defined as the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.2 Earlier prospective clinical trials have provided evidence that achieving uMRD in CLL patients is associated with improved clinical outcomes.2
“Chronic lymphocytic leukemia can relapse and become refractory to first-line treatment, and there is a need for better therapies to treat these patients who otherwise have limited options,” said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of Cancer Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. “The venetoclax plus rituximab combination provides these patients with an alternative treatment option that is superior to a type of chemoimmunotherapy and can achieve deep responses, as shown by MRD negativity rates in the peripheral blood and bone marrow, allowing for a fixed duration of treatment without the need for chemoimmunotherapy.”
CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.4 CLL accounts for approximately one third of new leukemia diagnoses.5
In September 2018, AbbVie announced the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus rituximab for the treatment of patients with R/R CLL.
“The approval of VENCLYXTO in combination with rituximab is an important step forward in providing patients with relapsed/refractory chronic lymphocytic leukemia a strong chance to live longer without their disease progressing,” said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. “We look forward to bringing VENCLYXTO to more patients with chronic lymphocytic leukemia, while continuing to further the research and development of therapies with the potential to transform the standards of care in blood cancers.”
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.
About the MURANO Trial
A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO trial. The trial was designed to evaluate the efficacy and safety of VENCLYXTO in combination with rituximab (N=194) compared with bendamustine in combination with rituximab (N=195). The median age of patients in the trial was 65 years (range: 22-85).1
The primary efficacy endpoint was investigator (INV)-assessed PFS. Median PFS with VENCLYXTO in combination with rituximab was not reached compared with 17.0 months for bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11-0.25; P<0.0001). The median follow-up was 23.8 months (range: 0.0 to 37.4). Additional efficacy endpoints included independent review committee (IRC)-assessed PFS, INV- and IRC-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), overall survival and rates of uMRD.1
The safety profile of the combination of VENCLYXTO plus rituximab is consistent with the known safety profile of each of the medicines alone. The most common adverse reactions (ARs; ≥20 percent) of any grade for VENCLYXTO in combination with rituximab were neutropenia, diarrhea and upper respiratory tract infection. In the VENCLYXTO in combination with rituximab arm due to any AR, discontinuation occurred in 16 percent of patients, dose reduction in 15 percent, and dose interruption in 71 percent. In the VENCLYXTO in combination with rituximab arm, neutropenia led to dose interruption of VENCLYXTO in 43 percent of patients and discontinuation in 3 percent. The most serious ARs (≥2 percent) for VENCLYXTO in combination with rituximab or VENCLYXTO monotherapy were pneumonia, febrile neutropenia and tumor lysis syndrome.1
About VENCLYXTO® (venetoclax)
VENCLEXTA® (VENCLYXTO® in the EU) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.
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. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.
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 Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
2 Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;806398.
3 Summary of Product Characteristics for VENCLYXTO. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG
4 NCI dictionary. NCI Dictionary of Terms. Chronic Lymphocytic Leukemia. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed September 2018.
5 World Health Organization. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf. Accessed September 2018.
SOURCE: AbbVie
Post Views: 49
– The approval is based on the MURANO Phase 3 clinical trial, in which VENCLYXTO® plus rituximab reduced the risk of disease progression or death by 83 percent and overall survival was prolonged compared to bendamustine in combination with rituximab, a standard of care chemoimmunotherapy regimen¹
– Majority of patients (62.4 percent) treated with VENCLYXTO plus rituximab achieved high rates of undetectable minimal residual disease (also known as minimal residual disease negativity) in peripheral blood compared to 13.3 percent of patients who received bendamustine plus rituximab¹
– Today’s approval makes VENCLYXTO plus rituximab the first chemotherapy-free combination with a 24-month fixed duration for the treatment of patients with chronic lymphocytic leukemia who have received at least one prior therapy
NORTH CHICAGO, IL, USA I November 1, 2018 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, announced today that the European Commission (EC) has approved the type-II variation application for VENCLYXTO® (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy. This approval allows more patients to receive VENCLYXTO in the second-line setting and gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union (EU). The approval is valid in all 28 member states of the EU, as well as Iceland, Liechtenstein and Norway.
The EC approval is based on results from the MURANO Phase 3 randomized clinical trial, which evaluated the efficacy and safety of VENCLYXTO in combination with rituximab compared to bendamustine in combination with rituximab, an established standard of care chemoimmunotherapy regimen for patients with R/R CLL.1 At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death2) in patients who received VENCLYXTO plus rituximab, resulting in an 83 percent reduction in the risk of disease progression or death (hazard ratio [HR]:0.17; 95% confidence interval [CI]: 0.11-0.25; P<0.0001) and prolonged overall survival (OS) compared to the standard of care chemoimmunotherapy (HR: 0.48; 95% CI: 0.25-0.90; overall survival data are not yet mature).1
In the MURANO Phase 3 clinical trial, undetectable minimal residual disease (uMRD) was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,3). The majority of patients in the trial who received VENCLYXTO plus rituximab achieved uMRD in the peripheral blood, with 62.4 percent of patients achieving uMRD versus 13.3 percent with bendamustine in combination with rituximab.1 uMRD is an objective measure defined as the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.2 Earlier prospective clinical trials have provided evidence that achieving uMRD in CLL patients is associated with improved clinical outcomes.2
“Chronic lymphocytic leukemia can relapse and become refractory to first-line treatment, and there is a need for better therapies to treat these patients who otherwise have limited options,” said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of Cancer Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. “The venetoclax plus rituximab combination provides these patients with an alternative treatment option that is superior to a type of chemoimmunotherapy and can achieve deep responses, as shown by MRD negativity rates in the peripheral blood and bone marrow, allowing for a fixed duration of treatment without the need for chemoimmunotherapy.”
CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.4 CLL accounts for approximately one third of new leukemia diagnoses.5
In September 2018, AbbVie announced the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus rituximab for the treatment of patients with R/R CLL.
“The approval of VENCLYXTO in combination with rituximab is an important step forward in providing patients with relapsed/refractory chronic lymphocytic leukemia a strong chance to live longer without their disease progressing,” said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. “We look forward to bringing VENCLYXTO to more patients with chronic lymphocytic leukemia, while continuing to further the research and development of therapies with the potential to transform the standards of care in blood cancers.”
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.
About the MURANO Trial
A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO trial. The trial was designed to evaluate the efficacy and safety of VENCLYXTO in combination with rituximab (N=194) compared with bendamustine in combination with rituximab (N=195). The median age of patients in the trial was 65 years (range: 22-85).1
The primary efficacy endpoint was investigator (INV)-assessed PFS. Median PFS with VENCLYXTO in combination with rituximab was not reached compared with 17.0 months for bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11-0.25; P<0.0001). The median follow-up was 23.8 months (range: 0.0 to 37.4). Additional efficacy endpoints included independent review committee (IRC)-assessed PFS, INV- and IRC-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), overall survival and rates of uMRD.1
The safety profile of the combination of VENCLYXTO plus rituximab is consistent with the known safety profile of each of the medicines alone. The most common adverse reactions (ARs; ≥20 percent) of any grade for VENCLYXTO in combination with rituximab were neutropenia, diarrhea and upper respiratory tract infection. In the VENCLYXTO in combination with rituximab arm due to any AR, discontinuation occurred in 16 percent of patients, dose reduction in 15 percent, and dose interruption in 71 percent. In the VENCLYXTO in combination with rituximab arm, neutropenia led to dose interruption of VENCLYXTO in 43 percent of patients and discontinuation in 3 percent. The most serious ARs (≥2 percent) for VENCLYXTO in combination with rituximab or VENCLYXTO monotherapy were pneumonia, febrile neutropenia and tumor lysis syndrome.1
About VENCLYXTO® (venetoclax)
VENCLEXTA® (VENCLYXTO® in the EU) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.
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. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.
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 Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.
2 Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;806398.
3 Summary of Product Characteristics for VENCLYXTO. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG
4 NCI dictionary. NCI Dictionary of Terms. Chronic Lymphocytic Leukemia. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed September 2018.
5 World Health Organization. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf. Accessed September 2018.
SOURCE: AbbVie
Post Views: 49
