NICE gives green light for chemotherapy-free combination, Venclyxto® (venetoclax) plus obinutuzumab for all front-line patients with chronic lymphocytic leukaemia – the UK’s most common chronic blood cancer

NICE gives green light for chemotherapy-free combination, Venclyxto® (venetoclax) plus obinutuzumab for all front-line patients with chronic lymphocytic leukaemia – the UK’s most common chronic blood cancer

• Positive recommendation for Venclyxto (venetoclax) means that all previously untreated patients with chronic lymphocytic leukaemia (CLL) will, for the first time, have a chemotherapy-free, fixed-duration treatment option¹
• NICE approval is based on data from Phase III CLL14 trial, which showed that 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 chemoimmunotherapy regimen of obinutuzumab and chlorambucil²
• CLL is the most common form of chronic leukaemia (blood cancer) in adults, with approximately 3,800 new cases in the UK each year^3,4

Maidenhead, UK, 10 November, 2020 – AbbVie (NYSE: ABBV) announced, from today and for the first time, people with chronic lymphocytic leukaemia (CLL) who have not received any prior treatment 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 chemoimmunotherapy.²

New guidance, published by The National Institute of Health and Care Excellence (NICE), recommends AbbVie’s venetoclax in combination with obinutuzumab for routine National Healthcare Service (NHS) use in patients with del(17p)/TP53 mutation and those without del(17p)/TP53 mutation for whom fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine and rituximab (BR) are unsuitable. In addition, NICE has also recommended the venetoclax combination for use within the Cancer Drugs Fund (CDF) for patients without del(17p)/TP53 mutation and for whom FCR or BR are suitable, subject to a managed access agreement.¹ The combination therapy will be available to NHS patients in England immediately.

CLL is the most common type of chronic blood cancer, with around 10 new patients diagnosed every day.^3,4 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.⁵ However, despite novel therapeutic advancements in CLL, the disease remains incurable and patients will often relapse following treatment.⁶

Professor Peter Hillmen, consultant in clinical haematology at Leeds Teaching Hospitals and honorary professor of haematology at University of Leeds, commented: “Today’s announcement means that healthcare professionals will now have the option to prescribe a first-line, chemotherapy-free, 1-year fixed duration treatment option for all patients with CLL, that can produce a deep response, thus allowing patients to stop treatment and achieve sustained progression-free survival post-treatment cessation. Ultimately, this has the potential to improve patients’ quality of life and reduce the significant burden of therapy.”

Marc Auckland, CLL patient and chair of the CLL Support Association, said: “NICE’s recommendation signifies an important evolution in the CLL treatment landscape. Simply put, what we have here is a novel treatment which provides very deep response rates with a fixed duration of treatment – this a welcome milestone for the CLL community.”

Belinda Byrne, medical director at AbbVie UK, added: “As a company, our mission is to have a remarkable impact on people's lives – and we know we cannot go it alone. We have worked closely with NICE, NHS England and the clinical and patient community to ensure all CLL patients have access to venetoclax in the frontline setting as quickly as possible. This decision recognises the benefit of venetoclax for both CLL patients and the NHS.”

The European Commission approved venetoclax plus obinutuzumab for the treatment of for adult patients with previously untreated chronic lymphocytic leukaemia in March 2020.⁷

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.

-End-

Date of preparation: November 2020                 

UK-VNCCLL-200321

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:

Jo Jones                                             Rupal Antoniou

+44 (0)7795 590344                       +44 (0)7870 678 084                                    

joanna.jones@abbvie.com           Rupal.Antoniou@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.⁸ 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.⁸

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

The Final Appraisal Document published by NICE today states that venetoclax plus obinutuzumab is recommended as an option for untreated chronic lymphocytic leukaemia (CLL) in adults, only if:

• there is a 17p deletion or TP53 mutation, or
• there is no 17p deletion or TP53 mutation, and fludarabine plus cyclophosphamide and rituximab (FCR), or bendamustine plus rituximab (BR), is unsuitable, and
• the company provides the drug according to the commercial arrangement

Venetoclax plus obinutuzumab is recommended for use within the Cancer Drugs Fund as an option for untreated CLL in adults, only if:

• there is no 17p deletion or TP53 mutation, and FCR or BR is suitable, and
• the conditions in the managed access agreement for venetoclax plus obinutuzumab are followed.

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.⁹

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.¹⁰

About the Phase 3 CLL14 Trial

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).¹¹ 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).8

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.co.uk. Follow @abbvieuk on Twitter.

References

1. National Institute for Health and Care Excellence. ID1402 Final Appraisal Document Venetoclax with obinutuzumab for untreated chronic lymphocytic leukaemia. November 2020. Available at: https://www.nice.org.uk/guidance/gid-ta10328/documents/final-appraisal-determination-document.
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. Leukaemia Care. Watch Wait Worry [online]. Available from: https://www.leukaemiacare.org.uk/our-campaigns/watch-wait-worry/ [Last accessed: November 2020].
6. 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].
7. 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]
8. 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].
9. 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].
10. 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.
11. 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.