AbbVie Receives Positive CHMP Opinion for a Novel, Chemo-free Combination of VENCLYXTO®▼ (venetoclax) with Rituximab as a Treatment with a Fixed Duration for Patients with Chronic Lymphocytic Leukemia Who Have Received at Least One Prior Therapy

• If approved by the European Commission (EC), venetoclax plus rituximab would be the first chemotherapy-free combination regimen with a fixed duration of treatment for patients with chronic lymphocytic leukemia who have received at least one prior therapy.
• The positive opinion is based on the MURANO Phase 3 clinical trial, in which venetoclax plus rituximab met the primary endpoint of prolonged progression-free survival and eighty-three percent (n=162/194) of patients achieved undetectable minimal residual disease in the peripheral blood, compared to twenty-three percent (n=45/195) with a standard of care chemoimmunotherapy regimen of bendamustine plus rituximab.¹
• The safety profile of the combination of venetoclax plus rituximab is consistent with the known safety profile of each medicine alone.¹

MAIDENHEAD, 21 September, 2018 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion for VENCLYXTO® (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy.The positive CHMP opinion is a scientific recommendation for marketing authorisation to the European Commission (EC), which will deliver its final decision, valid in all 28 member states of the European Union, as well as Iceland, Liechtenstein and Norway.

CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.2 Over 3,500 people are diagnosed with CLL in the UK each year and the incidence has risen by 18% in less than 30 years.³ For those patients living with CLL requiringtreatment, the majority will eventually have their disease recur.⁴ In the relapsed/refractory setting, there are currently limited treatments available. 50% of patients who fail on current treatments can face survival as short as three months.^5,6

Professor Peter Hillmen, Consultant Haematologist, Leeds Teaching Hospitals NHS Trust and Coordinating Investigator of venetoclax studies in the UK said; “The CHMP’s positive opinion of venetoclax plus rituximab is a key step towards the use of this novel combination for patients with relapsed/refractory chronic lymphocytic leukaemia in the UK, and underlines the significance of the MURANO phase three trial data. Venetoclax plus rituximab represents an important option for patients with relapsed and refractory CLL which is superior to a commonly used chemotherapy-based combination and prolongs progression-free survival. In addition, this new combination offers patients a fixed treatment duration allowing the cessation of therapy after two-years followed by a treatment-free interval.”

“This positive CHMP opinion is one important step forward as AbbVie continues to further the research and development of novel medicines with the potential to transform the standard of care in blood cancers,” said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. “The combination of venetoclax with rituximab has the potential to give patients with relapsed/refractory chronic lymphocytic leukemia a chance to live longer without their disease progressing, and to stop treatment after their two-year course.”

The CHMP positive opinion is based on results from the MURANO Phase 3 clinical trial, which evaluated the efficacy and safety of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab. At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death⁷) for patients who received venetoclax plus rituximab compared with bendamustine plus rituximab.¹

In the MURANO clinical trial, undetectable minimal residual disease (uMRD), also known as minimal residual disease negativity (MRD-) was a secondary endpoint. Eighty-three percent (n=162/194) of patients in the trial who received venetoclax plus rituximab achieved uMRD in the peripheral blood versus twenty-three percent (n=45/195) in the control group who received a standard of care chemoimmunotherapy regimen of bendamustine plus rituximab.¹ Undetectable minimal residual disease, 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.⁷

In 2016, venetoclax was approved by the EC as a monotherapy for the treatment of R/R CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, and for the treatment of CLL in the absence of these mutations in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.⁸

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. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other haematological cancers.^9,10,11,12

-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

For further information:

AbbVie UK Media:

Joanna Jones

07795590344

Joanna.jones@abbvie.com

Francesca Morley

07795360167

Francesca.Morely@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.⁸ Venetoclax in combination with rituximab is not currently approved for use in the UK.

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 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.

2. NCI dictionary. NCI Dictionary of Terms. Chronic Lymphocytic Leukemia. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed September 2018.

3. 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: September 2018.

4. American Cancer Society. (2013) Leukemia – Chronic Lymphocytic. Available at: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia.html. Accessed September 2018. 

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

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

7. 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. 

8. Venclyxto Summary of Product Characteristics. Available from: https://www.medicines.org.uk/emc/medicine/32650. Accessed September 2018. 

9. Clinicaltrials.gov. NCT01889186: A study of the efficacy of ABT-199 in subjects with relapsed or refractory chronic lymphocytic leukemia with the 17p deletion. Accessed May 2018.

10. Clinicaltrials.gov. NCT01994837: A Phase 2 study of ABT-199 in subjects with acute myelogenous leukemia (AML). Accessed May 2018. 

11. Clinicaltrials.gov. NCT01794520: Study evaluating ABT-199 in subjects with relapsed or refractory multiple myeloma. Accessed May 2018. 

12. Clinicaltrials.gov. NCT01328626: A Phase 1 study evaluating the safety and pharmacokinetics of ABT-199 in subjects with relapsed or refractory chronic lymphocytic leukemia and non-Hodgkin lymphoma. Accessed May 2018.