NICE recommends access to AbbVie’s VENCLYXTO®▼ (venetoclax) to treat most common form of adult leukaemia in England via Cancer Drugs Fund

MAIDENHEAD, UK, 5 OCTOBER 2017 – Today the National Institute for Health and Care Excellence (NICE) has issued a final appraisal determination (FAD) recommending that AbbVie’s VENCLYXTO® (venetoclax) is made available to NHS patients with difficult-to-treat types of chronic lymphocytic leukaemia (CLL) via the Cancer Drugs Fund (CDF), providing conditions of the managed access agreement are followed. Venetoclax will now be available on the NHS to adult patients in England with CLL in the absence of 17p deletion or TP53 mutation who have failed both chemo-immunotherapy and a B-cell receptor (BCR) inhibitor. Venetoclax has also been recommended for the treatment of adult CLL patients in the presence of 17p deletion or TP53 mutation who are either unsuitable for or have failed a BCR inhibitor.² Please see the NICE website for the eligibility criteria: https://www.nice.org.uk/guidance/gid-ta10077/documents/finalappraisal-determination-document.

Today’s recommendation marks the continuation of patient access across the UK, following the recent acceptance of venetoclax for use across NHS Scotland this August. 

“The immediate inclusion of venetoclax in the Cancer Drugs Fund is a positive step forward for patients with CLL in England” commented David Innes, Chair of the CLL Support Association. “Access to new treatment options is vital for patients with challenging forms of CLL, who have a short life expectancy after exhausting current treatment options. We are pleased to see AbbVie and NICE working together to expedite patient access and are hopeful that this will ultimately translate into longer-term routine prescribing on the NHS, providing an essential treatment option for those living with CLL and their families.”

Venetoclax, is a first-in-class, oral, once-daily medicine that selectively inhibits the function of the BCL-2 protein, restoring the body’s ability to trigger cancer cell self-destruction.² For those patients living with CLL requiring treatment, the majority will eventually have their disease recur,³ with one in two patients failing current treatments facing survival as short as three months.^4,5 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. 

Dr Peter Hillmen, Professor of Experimental Haematology and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust, commented, “Today’s recommendation is great news for patients with CLL who have failed existing treatments, and provides clinicians with an important new treatment option. The studies that NICE has assessed to reach this positive decision represent amilestone in the management of relapsed/refractory CLL. The early clinical data is compelling, showing survival benefits for this challenging group of patients, including some who achieved complete remission. I would anticipate that collection of further data through the CDF will confirm these extremely promising early findings.” 

Alice Butler, Medical Director at AbbVie, said, “We are pleased with today’s decision having worked closely with NICE, NHS England (NHSE) and the clinical and patient community to ensure that patients can gain access to venetoclax on the NHS. Working together with the NHS to collect more long-term data provides an important opportunity to understand the impact of venetoclax on the survival of patients with this difficult-to-treat type of CLL.” 

CLL affects the blood and immune system and is the most common form of adult leukaemia with almost 3,500 people affected in the UK each year, with over 3,000 cases in England alone. ^6,7 For people who develop or harbour gene mutations, such as 17p deletion and/or TP53 mutation, treatment is particularly challenging and these are associated with poorer quality of life and a median life expectancy of less than two to three years with current standard-of-care regimens. ^8,9 

In a Phase 2 study (M13-982) of 158 patients with relapsed and/or refractory CLL with a 17p deletion, the overall response rate was 77.2% (122/158) according to investigator assessment. ^10,11 Based on Kaplan-Meier estimations, 86.7% of patients were estimated to be alive following 12 months of treatment. ¹¹ In a separate Phase 2 two arm study (M14-032) of venetoclax in 64 CLL patients who relapsed or were refractory to BCR inhibitors (ibrutinib or idelalisib), the primary endpoint, overall response rate, was 67% and 57% respectively, according to investigator assessment. ¹¹ Venetoclax has also demonstrated early and sustained improvements in fatigue, a debilitating symptom of CLL, with reductions observed at just 4 weeks. ¹²

A recent study supports the use of Minimal Residual Disease (MRD) negativity as a prognostic marker for long-term progression-free survival and as a potential therapeutic goal in CLL. MRD negativity describes the presence of a small number of leukaemic cells that remain following treatment and is defined as <1 CLL cell detectable per 10,000 leukocytes.^13,14 In a Phase 2 study in patients with relapsing and refractory CLL with the del(17p) gene mutation, a high risk prognostic factor, MRD was used as an exploratory endpoint. Of 158 patients who were treated with venetoclax, 24% of patients (38/158) achieved MRD negativity in the peripheral blood, including 16 patients who were also MRD negative in the bone marrow. ¹¹ 

Venetoclax was the first blood cancer medicine to be given positive scientific opinion through the Early Access to Medicines Scheme (EAMS), following its designation as a Promising Innovative Medicine (PIM) by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) designation. ¹⁵

As part of AbbVie’s ongoing focus on delivering breakthrough medicines, it has worked with the MHRA and NHSE to provide 50 patients in the UK with early access to venetoclax via EAMS. Once EAMS ceased, AbbVie made a commitment to providing the treatment free of charge until reimbursement. Through a combination of EAMS and free of charge supply, approximately 100 patients with a high unmet need have benefitted from early access to venetoclax. 

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▼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 ukadverseevents@abbvie.com.

About VENCLYXTO® (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 some cancer types. Venetoclax, which is given once daily, is designed to selectively inhibit the function of the BCL-2 protein. ² 

Venetoclax is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialised by the companies in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to further BCL-2 research with venetoclax. 

The safety of venetoclax is based on pooled data of 296 patients treated with venetoclax in two Phase 2 studies and one Phase 1 study. ² In all, the studies enrolled patients with previously treated CLL, including 188 patients with 17p deletion and 92 patients who had failed a BCR inhibitor.² Patients were treated with venetoclax 400mg monotherapy once daily following a dose-titration schedule. The most commonly occurring adverse reactions (≥20 per cent) of any grade in patients receiving venetoclax were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, upper respiratory tract infection, fatigue, hyperphosphataemia, vomiting and constipation.² The most frequently reported serious adverse reactions (≥2 per cent) were pneumonia, febrile neutropenia and tumor lysis syndrome (TLS).² Discontinuations due to adverse reactions occurred in 9.1 per cent of patients. Dosage adjustments due to adverse reactions occurred in 11.8 per cent of patients.² 

TLS is an important identified risk when initiating venetoclax. TLS is caused by rapid killing of cancer cells. In 122 patients with CLL with a 20mg daily starting dose, the rate of TLS was three per cent. No TLS with clinical consequences such as acute renal failure, cardiac arrhythmias or sudden death and/or seizures was observed in these patients. ² This rate of TLS reflects the use of a dose ramp-up, starting with a daily dose of 20mg and increasing over five weeks to a daily dose of 400mg, as well as implementation of specific prophylaxis and monitoring measures during the ramp-up phase.²

References

¹ NICE Final Appraisal Determination. Venetoclax for treating chronic lymphocytic leukaemia: https://www.nice.org.uk/guidance/gid-ta10077/documents/final-appraisal-determination-document. Last accessed October 2017. 

² VENCLYXTO summary of product characteristics. https://www.medicines.org.uk/emc/medicine/32650. Last accessed October 2017.

³ American Cancer Society. (2013) Leukemia – Chronic Lymphocytic. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003111-pdf.pdf. Last accessed September 2017. 

⁴ Follows G. Outcomes for UK CLL patients post ibrutinib therapy. UK CLL Forum poster presented at BSH. 2017. 

⁵ Jain PW et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood. 2015; 125: 2062-2067. 

⁶ Macmillan. What is Chronic Lymphocytic Leukaemia. Available at: http://www.macmillan.org.uk/informationand-support/leukaemia/chronic-lymphocytic/understanding-cancer/about-cll.html. Last accessed September 2017. 

⁷ Cancer Research UK. Chronic lymphocytic leukaemia (CLL) statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemiacll/incidence#heading-Zero. Last accessed September 2017. 

⁸ Schnaiter A, et al. 17p deletion in chronic lymphocytic leukemia: risk stratification and therapeutic approach. Hematol Oncol Clin N Am. 2013; 27:289-301 

⁹ Stilgenbauer S, et al. Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2010; 1:481-488. 

¹⁰ Stilgenbauer S, et al. Venetoclax in relapsed/refractory chronic lymphocytic leukemia (CLL) with 17p deletion: outcome and minimal residual disease from the full population of the pivotal M13-982 trial. Presented at the 2017 European Hematology Association Congress, June 23, 2017. 

¹¹ Committee for Medicinal Products for Human Use (CHMP). Assessment report: Venclyxto. European Medicines Agency. EMA/725631, 2016. 

¹² Wierda, W. Interim quality of life results with venetoclax (ABT-199/GDC-0199) monotherapy in patients with relapsed/refractory del(17p) chronic lymphocytic leukaemia. 

¹³ Kwok M et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood Journal. 2016;128 (24): 2770-2774 

¹⁴ Kovacs et al. Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients with Chronic Lymphocytic Leukemia (CLL) Who Achieve Patial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. Journal of Clinical Oncology 2016;34 (31): 3758-3765 

¹⁵ MHRA. Early Access to Medicines Scientific Opinion - Public Assessment Report on venetoclax. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/547406/EAMS_Public_Asses sment_Report__-_Venetoclax.pdf. Last accessed September 2017

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Date of prep: October 2017