– VENCLYXTO® plus obinutuzumab is the first chemotherapy-free, fixed-duration combination regimen approved by the European Commission (EC) for patients with previously untreated chronic lymphocytic leukemia (CLL)
– Approval is based on data from the Phase 3 CLL14 trial, which showed that patients treated with obinutuzumab plus one year of treatment with VENCLYXTO had superior progression-free survival (PFS) and higher rates of undetectable minimal residual disease compared to patients receiving a standard of care chemoimmunotherapy regimen of obinutuzumab and chlorambucil[1],[5]
NORTH CHICAGO, IL, USA I March 12, 2020 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, announced today that the European Commission (EC) has approved VENCLYXTO® (venetoclax) in combination with obinutuzumab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who were previously untreated. The approval is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein, Norway and the United Kingdom.
“This approval underscores the growing utility of VENCLYXTO in treating CLL and demonstrates its clinical benefit as a chemotherapy-free combination therapy option for CLL patients in Europe who have not yet been treated,” said Neil Gallagher, M.D., Ph.D., chief medical officer and vice president of development. “We look forward to bringing VENCLYXTO to even more patients who can potentially benefit from achieving a deep response and sustained progression free survival, with the added benefit of a finite treatment duration.”
This is the third approval for VENCLYXTO, a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 is a protein that prevents cancer cells from undergoing apoptosis, the process that leads to the natural death or self-destruction of cancer cells. VENCLYXTO is also approved in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy, and as a monotherapy for the treatment of CLL in the presence or absence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor.
This most recent approval is based on results from the Phase 3 CLL14 clinical trial primary analysis (median follow up of 28 months), which demonstrated superior progression-free survival (PFS; the time on treatment without disease progression or death) as assessed by investigators in patients treated with VENCLYXTO plus obinutuzumab compared to patients who received a standard of care chemotherapy regimen of chlorambucil plus obinutuzumab (hazard ratio 0.35; 95% CI (0.23,0.53), p<0.0001, medians not yet reached). At an updated CLL14 efficacy analysis (median follow-up of 40 months), the median PFS had not been reached in the VENCLYXTO + obinutuzumab arm and was 35.6 months [95% CI: 33.7,40.7] in the obinutuzumab + chlorambucil arm (hazard ratio 0.31; 95% CI: 0.22, 0.44). The 36-month PFS estimate in the venetoclax plus obinutuzumab arm was 81.9% [95% CI: 76.5, 87.3] and in the obinutuzumab plus chlorambucil arm was 49.5% [95% CI: 42.4, 56.6]. Additionally, after completing one year of treatment, patients treated with the VENCLYXTO combination experienced deep response as measured by higher rates of undetectable minimal residual disease (MRD) or complete response (CR) as compared to patients receiving a standard of care regimen.1,5
In the trial, adverse events (AEs) were consistent with the known safety profiles of venetoclax and obinutuzumab alone. At least one AE of any grade occurred in 94.3% of patients in the venetoclax combination arm. The most common Grade 3/4 AEs were neutropenia and infections. Tumor lysis syndrome (TLS) was reported in three patients in the venetoclax plus obinutuzumab group (all during treatment with obinutuzumab and before venetoclax).1
“CLL is the most common of the nearly 95,000 new cases of leukemia in Europe each year, and chemotherapy is often the first line of treatment,” said Michael Hallek, M.D., lead investigator of the CLL14 study, director of the Department of Internal Medicine and Center of Integrated Oncology at the University Hospital Cologne in Germany, and head of the German CLL Study Group. “Having the option to utilize a first-line, chemotherapy-free treatment combination that can produce a deep response, thus allowing patients to stop treatment, will change the way we treat CLL and have a significant impact on patients.”
In January 2020, AbbVie announced that the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus obinutuzumab for the treatment of patients with previously untreated CLL.
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 Chronic Lymphocytic Leukemia
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. In 2018, approximately 95,000 new cases of leukemia were diagnosed in Europe.2 CLL is the most common form of leukemia in the Western Hemisphere, accounting for approximately one third of new leukemia diagnoses.3,4
About the CLL14 Trial
The randomized, multicenter, open-label, actively controlled 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 VENCLYXTO and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in patients with previously-untreated CLL and coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] score >6 or creatinine clearance <70 mL/min). The therapies were administered for a fixed duration of 12 cycles for VENCLYXTO in combination with six cycles of obinutuzumab. Cycles were comprised of 28 days. The trial enrolled 432 patients, all of whom were diagnosed according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and were previously untreated. The primary efficacy outcome was PFS as assessed by the investigator.1 Key secondary endpoints were MRD-negativity in peripheral blood and bone marrow, and overall and complete response rates.1
About VENCLYXTO® (venetoclax tablets)
VENCLYXTO® 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. VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.
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.
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.
VENCLYXTO (venetoclax) EU Indication and Summary of Important Safety Information5
Indication
Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
Venclyxto in combination with rituximab is indicated for the treatment of adult patients with 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 chemoimmunotherapy 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. AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 300 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 Fischer K, et al. Effect of fixed-duration venetoclax plus obinutuzumab (VenG) on progression-free survival (PFS), and rates and duration of minimal residual disease negativity (MRD–) in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) and comorbidities. Presented at the 2019 American Society of Clinical Oncology Annual Meeting: June 4, 2019; Chicago.
2 International Agency for Research on Cancer. World Health Organization. Europe Globocan 2018. https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf. Accessed February 2020.
3 NCI dictionary. NCI Dictionary of Terms. Chronic Lymphocytic Leukemia. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed January 2020.
4 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 January 2020.
5 Summary of Product Characteristics for VENCLYXTO. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.
SOURCE: AbbVie
