SMC Accepts Chemotherapy-free Combination Treatment VENCLYXTO®▼(venetoclax) Plus Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia

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PRESS RELEASE

SMC Accepts Chemotherapy-free Combination Treatment VENCLYXTO^®▼(venetoclax) Plus Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia

• For the first time in Scotland, certain people with untreated chronic lymphocytic leukaemia (CLL) will have access to a chemotherapy-free, 12-month fixed-duration treatment option.[1]
• Scottish Medicines Consortium (SMC) acceptance is based on data from the Phase III CLL14 trial, which showed patients treated with 1 year of treatment with venetoclax plus obinutuzumab had superior progression-free survival and sustained that benefit after stopping treatment, compared with those receiving a commonly used chemo-immunotherapy regimen of obinutuzumab and chlorambucil.[2]
• CLL is the most common form of adult leukaemia (blood cancer) in the UK and an estimated 2,100 people in Scotland live with the disease [3][4]^,[5],-[6]

MAIDENHEAD, UK, 14:00 on 7^th December 2020 – AbbVie (NYSE: ABBV) today announces that for the first time in Scotland, certain people with untreated chronic lymphocytic leukaemia (CLL) will now have access to a chemotherapy-free, 12-month fixed-duration treatment that has been demonstrated to improve outcomes, allowing patients to live significantly longer without their disease progressing, compared to those receiving a commonly used chemo-immunotherapy.²

CLL is the most common type of chronic blood cancer, with around 10 new patients diagnosed in the UK every day and an estimated 2,100 people in Scotland live with the disease.^3-6 Unlike some cancers, CLL has a highly variable clinical course so patients are usually left to ‘watch and wait’, after which some patients will be offered appropriate treatment.[7] However, despite novel therapeutic advancements in CLL, the disease remains incurable and patients will often relapse following treatment.[8]

In response to the decision, Dr Mike Leach, Consultant Haematologist at the Beatson West of Scotland Cancer Centre in Glasgow, said: “Chemoimmunotherapy is currently the first line treatment for most CLL patients, however, it may not be well tolerated in the elderly and in those who have other health issues. The availability of this non-chemotherapy fixed duration combination regimen means that clinicians in Scotland now have another treatment option for these CLL patients, that can offer deeper clinical response and extended remission as well as fewer chemotherapy-related side effects. This has the potential to make a real difference to the lives of our patients.”

Marc Auckland, CLL patient and Chair of the CLL Support Association, said: “The SMC’s decision to make the venetoclax plus obinutuzumab combination treatment available within NHS Scotland to this group of patients is welcome news to the CLL patient community. This new fixed one-year treatment offers patients the opportunity of prolonged remission off treatment, which can help them to stay in work and participate in family and social activities. This can have immense psychological benefits”

Belinda Byrne, Medical Director at AbbVie, commented, “Today’s decision is an important milestone for people with CLL. As a company that is passionate about improving patient outcomes in blood cancer, we are delighted with the SMC decision to bring venetoclax plus obinutuzumab to certain untreated patients in Scotland. CLL is an area where there is high unmet need and few treatment options available, so we are proud to be a part of improving the treatment landscape for this patient community.”

The European Commission approved venetoclax plus obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia in March 2020.[9]

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

- Ends –

UK-VNCCLL-200427

December 2020

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

▼Adverse events should be reported. 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 GBPV@abbvie.com.

AbbVie UK Media:

Natalie Bennett                                  Tabitha Grindrod

07818 428 074                                   07785 610 696

Natalie.Bennett@abbvie.com            Tabitha.Grindrod@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.[10] Venetoclax, which is an oral once-daily treatment, is designed to selectively inhibit the function of the BCL-2 protein restoring the death instinct in the cancerous cells.¹⁰

In March 2020, venetoclax received marketing authorisation for its third indication, granting venetoclax for use in previously untreated CLL.

About chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of chronic blood cancer and it affects the white blood cells.^3,4 In CLL, the material found inside some bones (bone marrow) produces too many white blood cells called lymphocytes that aren't fully developed and don't work properly. Over time this can cause a range of problems, such as an increased risk of picking up infections, persistent tiredness, swollen glands in the neck, armpits or groin, and unusual bleeding or bruising.[11]

CLL is associated with a highly heterogeneous disease; this is partly due to genetic abnormalities identified in CLL cells such as mutations of TP53 and/or deletions in chromosome 17p [del(17p)]. The presence of these abnormalities is associated with decreased survival and predict impaired response to chemoimmunotherapy [12]

About the Phase 3 CLL14 Trial²

The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (GCLLSG), evaluated the efficacy and safety of a combined regimen of venetoclax plus obinutuzumab (n=216) versus obinutuzumab plus chlorambucil (n=216) in previously untreated patients with CLL and coexisting medical conditions. The therapies were administered for a fixed duration of 12 months for venetoclax in combination with six cycles of obinutuzumab. The primary endpoint was PFS based on investigator assessment. Key secondary endpoints were PFS as assessed by an independent review committee, MRD-negativity in peripheral blood and bone marrow, overall and complete response rates (ORR and CR rates, respectively), MRD-negativity in complete response in peripheral blood and bone marrow, and overall survival (OS).

The trial confirmed sustained progression-free survival (PFS) of the venetoclax combination versus obinutuzumab plus chlorambucil.² At three years, in an updated efficacy analysis, the estimated PFS rate for the venetoclax combination was 81.9 percent, compared to the PFS of 49.5 percent for patients taking commonly used chemoimmunotherapy chlorambucil-obinutuzumab (ClbG). Median PFS with venetoclax combination (n=216) was not reached and was 35.6 months with ClbG (n=216).[13] The most common adverse reactions in the venetoclax studies were neutropenia, diarrhea and upper respiratory tract infection. The most frequently reported serious reactions were pneumonia, sepsis, febrile neutropenia and tumor lysis syndrome (TLS).¹⁰

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 https://www.abbvie.co.uk/our-science/therapeutic-focus-areas/Oncology.html

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.co.uk. Follow @abbvieuk on Twitter.

References

[1]Scottish Medicines Consortium Final Advice SMC2293. Venetoclax in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL. Available at: https://www.scottishmedicines.org.uk/about-us/latest-updates/december-2020-decisions-news-release/

[2] 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; 4 June, 2019; Chicago, IL.

[3] Cancer Research UK. Chronic lymphocytic leukaemia (CLL) incidence statistics [online]. Available from:

https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-  cll/incidence [Last accessed: November 2020].

[4] Cancer Research UK. Chronic lymphocytic leukaemia (CLL): Risks and causes [online]. Available from:  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/risks-causes [Last accessed: November 2020].

[5] Public Health Scotland. Cancer Statistics. Available at: https://www.isdscotland.org/Health-Topics/Cancer/Cancer-Statistics/Leukaemias/#lymphocytic [Last accessed November 2020]

[6] Office for National Statistics. Population estimates for the UK, England and Wales, Scotland, and Northern Ireland: mid-2017. Available at:

https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/bulletins/annualmidyearpopulationestimates/mid2017. [Last accessed November 2020]

[7] Leukaemia Care. Watch Wait Worry [online]. Available from: https://www.leukaemiacare.org.uk/our-campaigns/watch-wait-worry/ [Last accessed: November 2020].

[8] Leukaemia Care. Relapse in Chronic Lymphocytic Leukaemia [online]. Available from:

https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Chronic-Lymphocytic-Leukaemia-CLL-Web-Version.pdf [Last accessed: November 2020].

[9] AbbVie Receives European Commission Approval of VENCLYXTO® Combination Regimen for Patients with Previously-Untreated Chronic Lymphocytic Leukemia. Available at https://news.abbvie.com/news/press-releases/abbvie-receives-european-commission-approval-venclyxto-combination-regimen-for-patients-with-previously-untreated-chronic-lymphocytic-leukemia.htm [Last accessed: November 2020]

[10] AbbVie Inc. Venclyxto (venetoclax): Summary of Product characteristics [online]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/venclyxto [Last accessed: November 2020].

[11]Cancer Research UK. Chronic lymphocytic leukaemia (CLL): Symptoms [online]. Available from: https://about-cancer.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/symptoms?_ga=2.125671690.1252676353.1598024288-774188295.1581519429 [Last accessed: November 2020].

[12] Eichhorst B, Robak T, Montserrat E et al. on behalf of the European Society for Medical Oncology (ESMO) Guidelines Committee (2015). Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 26 (S5): v78-v84.

[13] Al-Sawaf O, Zhang C, Tandon M, et al. Fixed-Duration Venetoclax-Obinutuzumab For Previously Untreated Chronic Lymphocytic Leukemia: Follow-Up of Efficacy and Safety Results from the Multicenter, Open-Label, Randomized Phase 3 CLL14 Trial. Poster presented at the virtual 25th European Hemotology Association (EHA) Annual Conference; 11–21 June 2020.