AbbVie Presents New Long-Term Data From VENCLYXTO®▼ (venetoclax) Chemotherapy-Free Combination Regimen in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

• Four-year updated analysis from the MURANO trial showed an 81% reduction in the risk of disease progression or death in patients treated with venetoclax plus rituximab (VenR) and higher rates of undetectable minimal residual disease (uMRD) compared to bendamustine plus rituximab(BR)1

• Sustained overall survival (OS) benefit was demonstrated with VenR over BR (with a hazard ratio of 0.41), despite 79% of patients in the BR arm who went on to receive a novel targeted treatment. Median OS was not reached for either treatment group1

• 68% of the 130 patients who completed the treatment course were free of disease progression and maintained OS benefit 24 months after being off venetoclax therapy1

• Full results are being highlighted today in an oral presentation at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition

MAIDENHEAD,UK, December 8, 2019 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today presented long-term data from a post-hoc analysis further supporting the clinical benefit of a fixed treatment duration with venetoclax in combination with rituximab (VenR) in patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) compared with a standard of care regimen of bendamustine plus rituximab (BR). The updated data from the Phase 3 MURANO trial four-year analysis (median follow-up of 48 months with all patients off venetoclax treatment for a median of 22 months) showed that patients with R/R CLL who completed the chemotherapy-free combination regimen of venetoclax plus rituximab with a two year fixed treatment duration maintained progression-free survival (PFS) and overall survival (OS) compared to BR.1

Patients who completed treatment with the venetoclax combination also achieved higher rates of uMRD and complete remissions compared to those treated with bendamustine plus rituximab.1 uMRD is 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. The full results were presented today at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition (abstract h#355).

“These results support the benefits of a fixed duration of treatment with venetoclax and rituximab to reduce the risk of disease progression or death in patients with chronic lymphocytic leukemia,” said Mohammed Zaki, M.D., Ph.D., vice president, global head of hematology development at AbbVie. “We remain committed to understanding the full utility of venetoclax combinations.”

“In the four-year analysis from the MURANO trial, treatment with the venetoclax combination resulted in an 81 percent reduction in the risk of progression or death compared to the standard of care,” said Professor John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and director of the Department of Hematology at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital in Australia. “The sustained efficacy and manageable safety profile observed in the study further support the clinical benefits of fixed treatment in patients with relapsed or refractory chronic lymphocytic leukemia.”

In the post-hoc analysis, median follow-up for patients who completed two years of treatment with venetoclax plus rituximab without progressive disease (n=130) was 22 months (range: 1 to 35 months). PFS (HR, 0.19, 95% CI: 0.14, 0.25, descriptive p<0.0001) and OS (HR 0.41, 95% CI: 0.26, 0.65, descriptive p<0.0001) was sustained for patients taking VenR compared to those taking BR. 24 months after patients were off therapy, the investigator (INV)-assessed estimated PFS was 68.0% (95% CI 57.6, 78.4). Additionally, the four year OS was 85.3% (95% CI: 89.2, 99.0) in the venetoclax arm compared to 66.8% for BR (medians not reached). Improvements in both PFS and OS were observed in the VenR arm despite 79% of patients in the control arm receiving an additional targeted CLL treatment after disease progression.1

By the end of treatment, 64% of patients had achieved uMRD, and 87% of those patients remained free of disease progression two years post-treatment.1 Achieving uMRD was assessed as a secondary endpoint because it is associated with improved clinical outcomes.2 Higher rates of uMRD were observed off treatment in patients taking VenR than in those taking standard of care BR.1

The safety profile of the combination is consistent with the known safety profile of each individual therapy alone. There were no new serious safety issues observed in the MURANO study since the last update. Excluding non-melanoma skin cancer, there was one report of melanoma in the standard of care cohort, and one report of melanoma and one report of breast cancer in the venetoclax combination cohort.1

Venetoclax, a first-in-class oral B-cell lymphoma-2 (BCL-2) inhibitor, is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of Roche Group, in the U.S. and by AbbVie outside the U.S.

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For venetoclax’s Summary of Product Characteristics, please visit: https://www.medicines.org.uk/emc/medicine/32650.

▼Adverse events should be reported. This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product.

Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AbbVie UK Ltd. Please contact uk_pvvendor@abbvie.com

AbbVie UK Media: 

Joanna Jones 

07795590344

Joanna.jones@abbvie.com

Francesca Morley

07795360167

Francesca.Morley@virgohealth.com

Notes to editors

Design and Results of MURANO Phase 3 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 venetoclax 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 to 85).3

The primary efficacy endpoint was INV-assessed PFS. At the time of the primary analysis, median PFS with venetoclax 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). In the primary efficacy analysis, the median follow-up for PFS was 23.8 months (range: 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), OS and rates of MRD-negativity.3

About venetoclax

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. Venetoclax targets the BCL-2 protein and works to help restore the process of apoptosis.

Venetoclax is approved in more than 50 countries, including the U.S. AbbVie, in collaboration with Roche, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

In January 2019, venetoclax in combination with rituximab was recommended by NICE (The National Institute for Health and Care Excellence) for the treatment of relapsed/refractory CLL on the NHS. Following this, VenR was accepted by the SMC (Scottish Medicines Consortium) for use by the NHS in Scotland in August 2019. These decisions were based on the pivotal results from the Phase 3 MURANO clinical trial. It is the first 24-month fixed treatment duration, chemotherapy-free combination approved for use in this patient population.4

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 tumour types. For more information, please visit www.abbvie.co.uk/our-science/therapeutic-focus- areas/Oncology.html

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.co.uk. Follow @abbvieuk on Twitter.

References

1. Seymour JF, et al. Four-Year Analysis of Murano Study Confirms Sustained Benefit of Time-Limited Venetoclax- Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL). Presented at the 2019 American Society of Hematology Annual Meeting & Exposition: December 8, 2019; Orlando.

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. 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.

4. National Institute for Health and Care Excellence. Venetoclax with rituximab for previously treated chronic lymphocytic leukaemia. 2019. Available at: https://www.nice.org.uk/guidance/ta561/chapter/1-Recommendations