– Positive opinion based on data from the VIALE-A and M14-358 trials, which evaluated the safety, efficacy and pharmacokinetics of VENCLYXTO in combination with hypomethylating agents in adult patients with AML
– Represents the third positive CHMP opinion for an extension of indications for VENCLYXTO; supports growing utility of this therapy across multiple hematologic malignancies
– Acute myeloid leukemia is a difficult-to-treat blood cancer, and the most common type of acute leukemia in the world
NORTH CHICAGO, IL, USA I April 23, 2021 I AbbVie (NYSE: ABBV) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for VENCLYXTO® (venetoclax) in combination with hypomethylating agents for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The positive CHMP opinion is a scientific recommendation for marketing authorization to the European Commission (EC), which is expected to deliver its final decision on VENCLYXTO combination therapy for use in AML in the first half of 2021.
The positive CHMP opinion represents the third for an extension of indications for VENCLYXTO. The opinion is based on results from the double-blind, placebo-controlled VIALE-A (M15-656) and the Phase 1b open-label, nonrandomized, multicenter M14-358 trial.
“This positive CHMP opinion for VENCLYXTO in acute myeloid leukemia is a critical step to providing new therapeutic options in the European Union for patients with this devastating disease,” said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development at AbbVie. “Enabling improved outcomes including potentially prolonging the lives of patients with malignant diseases such as acute myeloid leukemia is part of our mission and an objective we pursue relentlessly every day.”
AML is the most common acute leukemia in the world.1 An estimated 160,000 people are currently living with the disease globally. 1 The rate of new cases of acute myeloid leukemia is 4.3 per 100,000 men and women per year.3 It is also among the most difficult blood cancers to treat.2 Despite advances in available therapies and care, the five-year survival rate for patients diagnosed with AML remains approximately 29 percent.3 AML typically worsens quickly, and due to age and comorbidities, not all patients can tolerate intensive chemotherapy.4
“AML is an incredibly aggressive form of cancer, and patients who are diagnosed with this disease are often so ill that they cannot tolerate the intensive chemotherapy that healthcare providers would typically prescribe,” said Hartmut Döhner, M.D., Professor of Medicine and Director, Department of Hematology, Oncology, Palliative Care, Rheumatology and Infectious Diseases at University Hospital in Ulm, Germany. “VENCLYXTO combination therapy is a promising advancement for patients and their healthcare providers facing this challenging, lethal form of cancer.”
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 the VENCLYXTO AML Clinical Trial Program
AbbVie’s clinical trial program to evaluate VENCLYXTO combination therapy in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy included two studies conducted around the world.
VIALE-A (M15-656) Phase 3 Trial
The randomized, double-blind, placebo-controlled VIALE-A (M15-656) trial evaluated the efficacy and safety of VENCLYXTO in combination with azacitidine in patients with newly diagnosed AML who were ineligible for intensive chemotherapy. The study met its primary endpoints of statistically significant improvement of overall survival (OS) and complete remission rate and complete remission with incomplete hematologic recovery (CR + CRi). OS was 14.7 months for the VENCLYXTO plus azacitidine arm versus 9.6 months in the placebo plus azacitidine arm. The study also met secondary endpoints, with the VENCLYXTO plus azacitidine arm resulting in a CR rate of 36.7 percent vs. 17.9 percent in the placebo plus azacitidine arm and a composite complete remission rate (CR + CRi) of 66.4 percent versus 28.3 percent. The safety profile of VENCLYXTO plus azacitidine was consistent with the known side-effect profiles of both agents, and adverse events (AEs) were consistent with expectations for an older AML population; no differences between the two treatment arms with respect to quality-of-life measures were seen. The most frequently reported serious AEs in the VENCLYXTO plus azacitidine arm and placebo plus azacitidine arm were febrile neutropenia (in 30 percent and 10 percent), pneumonia (in 17 percent and 22 percent), sepsis (in 6 percent and 8 percent), and haemorrhage (in 9 percent and 6 percent).5
M14-358 Phase 1b Trial
The non-randomized, open-label M14-358 trial evaluated VENCLYXTO in combination with azacitidine or decitabine in patients with newly diagnosed AML. The trial showed patients treated with VENCLYXTO in combination with azacitidine achieved a CR rate of 44 percent and a CR+CRi rate of 71 percent. The median duration of response for patients treated with VENCLYXTO in combination with azacitidine who achieve a CR or CRi was 21.9 months. Median time to first CR or CRi was 1.2 months (range: 0.7 to 7.7 months). Patients who received VENCLYXTO in combination with decitabine achieved a CR rate of 55 percent and a CR+CRi rate of 74 percent. The median duration of response for patients treated with VENCLYXTO in combination with decitabine who achieved a CR or CRi was 15 months. Median time to first CR or CRi was 1.9 months (range: 0.9 to 5.4 months). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with azacitidine were febrile neutropenia (31 percent) and pneumonia (26 percent). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with decitabine were febrile neutropenia (42 percent), pneumonia (29 percent), bacteraemia (16 percent) and sepsis (6 percent).6
About VENCLYXTO® (venetoclax)
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. VENCLYXTO targets the BCL-2 protein and works to help 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. Venetoclax is approved in more than 80 countries, including the U.S.
Indication and Important VENCLYXTO (venetoclax) EU Safety Information7
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 are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie’s mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
1 Puty, T.C., Sarraf, J.S., Do Carmo Almeida, T.C. et al. Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol. Syst Rev 8, 109 (2019).
2 American Cancer Society (2018). Typical Treatment of Most Types of Acute Myeloid Leukemia (Except Acute Promyelocytic M3). https://www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html.
3 National Cancer Institute (2018). Acute Myeloid Leukemia – SEER Stat Fact Sheets. https://seer.cancer.gov/statfacts/html/amyl.html.
4 Pettit, K and Odenike, O. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies. Front Oncol. 2015; 5:250.
5 DiNardo, C.D., Jonas, B.A., et al. A Randomized, Double-Blind, Placebo-Controlled Study of Venetoclax With Azacitidine Vs. Azacitidine In Treatment-Naïve Patients with Acute Myeloid Leukemia Ineligible For Intensive Therapy: The Phase 3 VIALE-A Trial. (2020).
6 DiNardo CD, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018; 19(2):216-228.
7 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.
SOURCE: AbbVie
