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AbbVie Presents Data from VENCLYXTO®▼(venetoclax) Chemotherapy-Free Combination Regimen for Patients with Previously Untreated Chronic Lymphocytic

Press release   •   Jun 04, 2019 16:43 BST

  • Phase 3 CLL14 data were highlighted in an oral presentation (abstract #7502) today at ASCO and published in the New England Journal of Medicine
  • Patients treated with venetoclax plus obinutuzumab lived significantly longer without their disease progressing, and sustained that benefit after stopping treatment, compared to those treated with obinutuzumab plus chlorambucil
  • Rates of undetectable minimal residual disease* in peripheral blood were higher in patients treated with venetoclax plus obinutuzumab three months after treatment completion1

MAIDENHEAD, UK, 4 June, 2019 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today presented data from the CLL14 trial, the first randomised clinical trial to examine stopping an oral-based, chemotherapy-free combination after 12 months in previously untreated patients with CLL and coexisting medical conditions. The results demonstrate that venetoclax plus obinutuzumab prolonged progression-free survival (PFS) and achieved higher rates of complete response and undetectable minimal residual disease (uMRD) compared to a commonly used chemoimmunotherapy obinutuzumab plus chlorambucil.1

These data were presented today in an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (abstract #7502) and were simultaneously published in the New England Journal of Medicine (NEJM). *Undetectable minimal residual disease (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.2

Dr Angus Broom, Consultant Haematologist at the Western General Hospital in Edinburgh and CLL14 Study Investigator, said: “The results of the Phase 3 CLL14 clinical trial, presented today at the annual American Society of Clinical Oncology and published in the prestigious New England Journal of Medicine (NEJM), highlight that a one year fixed treatment duration of venetoclax plus obinutuzumab induces a longer time without disease progression compared to a commonly used chemoimmunotherapy, in previously untreated, unfit CLL patients. Improved progression-free survival with this chemotherapy-free regimen was also demonstrated after stopping treatment, as well as higher rates of uMRD, compared to obinutuzumab plus chlorambucil.”

CLL is the most common form of adult leukaemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.3,4. Over 3,500 people are diagnosed with CLL in the UK each year.5 The average age of CLL diagnosis is 72 years and almost 90% of CLL patients have one or more co-morbidities.3,6 Although many patients diagnosed with CLL will be put on a ‘Watch and Wait’ management strategy, around two thirds will eventually require treatment.7

In the CLL14 trial, investigator-assessed results demonstrated that patients with CLL who were treated with venetoclax plus obinutuzumab achieved superior PFS compared to patients treated with obinutuzumab plus chlorambucil. Twenty-four-month PFS estimates were 88.2 percent and 64.1 percent, respectively (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23, 0.53; P<0.0001). Higher rates of uMRD were observed with venetoclax plus obinutuzumab compared to obinutuzumab plus chlorambucil in both peripheral blood (75.5 percent versus 35.2 percent, P<0.0001) and bone marrow (56.9 percent versus 17.1 percent [P<0.0001]) three months after treatment completion.1 uMRD in the blood or bone marrow is an important therapeutic goal in patients with CLL as it can be associated with prolonged PFS and overall survival (OS).Complete response rates were also significantly higher with venetoclax plus obinutuzumab than with chlorambucil plus obinutuzumab (49.5 percent versus 23.1 percent [P<0.0001]).1

"Conducting CLL14 was another collaborative and bold attempt to continue pushing the boundaries of treatment in CLL,” said Mohamed Zaki, M.D., Ph.D., vice president, global head of hematology development, AbbVie. “The combination of venetoclax plus obinutuzumab significantly prolonged progression-free survival and patients maintained that benefit after stopping treatment. After the recent approval in the U.S., we look forward to continue working with health authorities worldwide as we aim to bring venetoclax plus obinutuzumab to patients with previously untreated CLL.”

In the CLL14 trial, the safety profile of both treatment groups showed no new safety signals or increase in known toxicities.1

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

- Ends -

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

About the Phase 3 CLL14 Trial

The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial evaluated the efficacy and safety of a combined investigational regimen of venetoclax plus obinutuzumab (n=216) versus obinutuzumab plus chlorambucil (n=216) in previously untreated patients with CLL and coexisting medical conditions. The trial was conducted in close collaboration with the German CLL Study Group (DCLLSG). The therapies were administered for a fixed duration of 12 months for venetoclax in combination with six cycles of obinutuzumab. The trial enrolled 432 patients, all of whom were previously untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. The primary endpoint was PFS based on investigator assessment, using iwCLL criteria.1

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, MRD-negativity in complete response in peripheral blood and bone marrow, and overall survival (OS).1

In the CLL14 trial, the safety profile of both treatment groups showed no new safety signals or increase in known toxicities. At least one AE of any grade occurred in 94.3 percent of patients in the venetoclax plus obinutuzumab arm. The most common Grade 3/4 AEs in patients receiving venetoclax plus obinutuzumab were febrile neutropaenia (5.2 percent) and infections (17.5 percent). Tumor lysis syndrome (TLS) was reported in three patients in the venetoclax plus obinutuzumab group (all during treatment with obinutuzumab and before venetoclax).1 None of these events met the Howard criteria for clinical TLS.9

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 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, 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.11

In May 2019, the U.S. Food and Drug Administration approved venetoclax in combination with obinutuzumab for previously untreated patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)12. The efficacy and safety of venetoclax in patients with newly diagnosed CLL has not been evaluated by the European Medicines Agency.

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

Fischer K, Al-Sawaf, Bahlo J, et al. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. New England Journal of Medicine. 2019. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1815281?query=main_nav_lg. Accessed: June 2019. 

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; 131(25):2745-2760

3 London Cancer. Chronic Lymphocytic Leukaemia. Available at: http://www.londoncancer.org/media/123091/Chronic-Lymphocytic-Leukaemia_London-Cancer-Guidelines.pdf. Available at: April 2019

4 National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available at: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed: April 2019

5 Cancer Research UK. Chronic lymphocytic leukaemia (CLL) incidence statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-cll/incidence. Accessed: April 2019

6 Schuh A H, Parry-Jones N, Appleby N et al. Guidelines for the treatment of Chronic Lymphocytic Leukaemia. British Journal of Haematology. 2018

7 Leukaemia Care. Watch Wait Worry. Available at: https://www.leukaemiacare.org.uk/get-involved/our-campaigns/watch-wait-worry/. Accessed: April 2019

Bottcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30(9):980-988.

9 Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J M 2011;364:1844-1854

10 Venclyxto Summary of Product Characteristics. Available from: https://www.medicines.org.uk/emc/medicine/32650. Accessed: April 2019

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

12 U.S. Food & Drug Administration. FDA approves Venetoclax for CLL and SLL. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll. Accessed: May 2019