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AbbVie Presents New Data from Phase 3 MURANO Trial of VENCLYXTO®▼ (venetoclax) in Combination with Rituximab in Patients with Relapsed/Refractory CLL Who Completed the Fixed Treatment Course

Press Release   •   Dec 01, 2018 22:45 GMT

– The data demonstrated that VENCLYXTO® in combination with rituximab (VenR) reduced the risk of disease progression or death compared to a standard of care bendamustine plus rituximab (BR) after a median three-year follow-up1

– Of the 130 patients who completed rituximab plus the 24-month fixed duration of venetoclax and remained off therapy for a median of 9.9 months, the estimated Progression Free Survival (PFS) rate at six and 12 months were 92 percent and 87 percent, respectively1

– Three-year estimated overall survival (OS) was 87.9 percent in patients treated with VenRversus 79.5 percent in patients receiving BR1

– Full results were presented today during the 60th American Society of Hematology (ASH) Annual Meeting & Exposition

MAIDENHEAD, 1ST December, 2018 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company today presented updated data from the pivotal Phase 3 MURANO trial of venetoclax (VENCLYXTO®) in combination with rituximab (VenR). The results at median follow-up of 36 months demonstrated continued substantial benefit with PFS and OS for patients with relapsed/refractory chronic lymphocytic leukaemia (R/R CLL), treated with VenR having completed the fixed duration of therapy and stopped treatment, compared to patients treated with a standard of care regimen of bendamustine plus rituximab (BR).1 The estimated PFS rate in those 130 patients at 36 months was 71.4 percent (95% confidence interval [CI]: 0.64, 0.78) for patients treated with VenR compared with 15.2 percent (95% CI: 0.09, 0.21) for patients who completed treatment with a standard of care combination of BR (hazard ratio [HR]:0.16; 95% CI: 0.12, 0.23).1 The data were presented today during the 60th American Society of Hematology (ASH) Annual Meeting & Exposition.

Of the 130 patients who completed the two-year treatment course of venetoclax and remained off therapy for a median of 9.9 months (range: 1.4 to 22.5), six- and 12-month PFS estimates were 92 percent (95% CI: 0.87, 0.96) and 87 percent (95% CI: 0.81, 0.93), respectively. 1 At the time of analysis, the overall survival (OS) benefit estimated at three years was 8 percent higher in the VenR arm (87.9 percent) than in the BR arm (79.5 percent) (HR: 0.50; 95% CI: 0.30, 0.85).1

“There is a need for a chemo-free option with a fixed treatment duration that can potentially provide prolonged progression-free survival, along with minimal residual disease negativity, in patients with relapsed or refractory chronic lymphocytic leukaemia,” said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of the Department of Hematology at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. “The results of this analysis showed that a high proportion of patients with relapsed or refractory chronic lymphocytic leukaemia who were treated with venetoclax in combination with rituximab maintained minimal residual disease negativity and progression-free survival well after completing the fixed treatment duration.”

In the MURANO clinical trial, 78 percent of patients who completed the two-year treatment course of VenR without disease progression (N=114) also demonstrated minimal residual disease (MRD)-negativity in peripheral blood.1 MRD-negativity was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,2,3). MRD-negativity (also known as undetectable MRD) 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.4 Earlier prospective clinical trials in CLL patients have provided evidence that achieving MRD-negativity is associated with improved clinical outcomes.5

“This analysis of the MURANO clinical trial showed that after patients had completed rituximab and a two-year course of venetoclax, and were off treatment for a median of 9.9 months, the disease did not progress in a substantial number of patients with relapsed or refractory chronic lymphocytic leukaemia, and in many of those patients the disease was undetectable in peripheral blood,” said Neil Gallagher, M.D., Ph.D., Head of Global Oncology Development, AbbVie. “These findings continue to support the use of venetoclax plus rituximab as a treatment with a fixed duration for patients with relapsed or refractory chronic lymphocytic leukaemia and are encouraging as we continue to advance the research and development of transformative medicines in blood cancers.”

Safety data were consistent with the known safety profiles of each medicine alone. During the venetoclax single-agent treatment phase (N=171), 10 percent of patients had an adverse event (AE) leading to drug withdrawal, 4 percent had an AE leading to dose reduction, 26 percent had an AE leading to dose interruption, and 4 percent had a fatal AE (four other cancers, two cardiac, one pneumonia). Grade 3/4 AEs occurred in 35 percent of patients. The most common Grade 3/4 AEs were neutropenia (12 percent), anaemia (3 percent) and thrombocytopenia (2 percent). Seven percent of patients had a Grade 3/4 infection during the single-agent phase.1

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

-Ends -

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

For the CHMP positive opinion for venetoclax in combination with rituximab, please visit: https://www.ema.europa.eu/documents/smop/chmp-summary-positive-opinion-venclyxto-ii/08_en.pdf

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

For further information:

AbbVie UK Media:

Joanna Jones

07795590344

Joanna.jones@abbvie.com

Francesca Morley

07795360167

Francesca.Morley@virgohealth.com

Notes to editors

About venetoclax
Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor. The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells. Venetoclax, which is an oral once-daily treatment, is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax in combination with rituximab is not currently approved for use in the UK.3

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.

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 J, et al. MURANO trial establishes feasibility of time-limited venetoclax-rituximab (VenR) combination therapy in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at the 2018 American Society of Hematology Annual Meeting & Exposition: December 1, 2018; San Diego.

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.

4. 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.

5. 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.