New VENCLYXTO®▼(venetoclax) Data Demonstrate Utility Across Acute Myeloid Leukaemia (AML) Patients and Chronic Lymphocytic Leukaemia (CLL)

  • Phase III VIALE-A study showed a 34% reduction in the risk of death in AML patients who were ineligible for intensive chemotherapy treated with venetoclax plus azacitidine compared with azacitidine plus placebo1
  • Patients in the venetoclax arm showed improved median overall survival (14.7 months) versus azacitidine alone (9.6 months) and improved rate of composite complete remission (CR + CRi) (66.4%) versus those treated with azacitidine alone (28.3%)1
  • Notable data in CLL patients include Phase III results from the CLL14 trial2 and Phase III sub-analysis from the MURANO trial3

Maidenhead, UK, 13 June 2020 – AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced the positive results from the VIALE-A (M15-656) trial. They demonstrated that previously untreated patients with acute myeloid leukaemia (AML) who were ineligible for intensive chemotherapy treated with VENCLYXTO® (venetoclax) plus azacitidine (n=286) achieved a 34% reduction in the risk of death compared with azacitidine in combination with placebo (n=145) (hazard ratio [HR] = 0.66 [95% confidence interval {CI}: 0.52–0.85]; P=0.001).1

The study met its primary endpoints of statistically significant improvement of overall survival (OS), with the patients in the venetoclax combination arm achieving improved median OS (14.7 months versus 9.6 months in the placebo arm). The study also met its secondary endpoints of composite complete remission [complete remission (CR) + CR with incomplete count recovery (CRi)], with the venetoclax combination arm resulting in a CR rate of 36.7% (versus 17.9% in the placebo arm), a CR with partial hematologic recovery (CRh) rate of 64.7% (versus 22.8% versus the placebo arm) and a composite complete remission rate (CR + CRi) of 66.4% (versus 28.3% in the placebo arm).1

The study observed a safety profile generally consistent with the known safety profiles of venetoclax combined with azacitidine and of the two medications alone.1

AML is the most common acute blood cancer in the world.4 In the UK alone, there are around 3,200 new cases every year, that is more than eight every day.5 AML is also one of the most aggressive and difficult-to-treat blood cancers. It spreads quickly, and due to age and comorbidities, not all patients are eligible to receive intensive chemotherapy.6 Only approximately 28% of patients will survive 5 years or more.7

“I am greatly encouraged by the VIALE-A data, which demonstrate that the venetoclax-azacitidine combination could have the potential to significantly improve the lives of people with AML who aren’t eligible for intensive chemotherapy,” said Belinda Byrne, Medical Director at AbbVie UK.

“As a company, we’re very proud of the data being presented at this year’s EHA meeting, which highlights the broad utility of venetoclax in treating the blood cancers AML and CLL. These data are a testament to our commitment to discovering and developing medicines that drive transformational improvements in blood cancer treatment.”

Venetoclax is not currently licensed for AML in the UK. These Phase III data will be submitted to global regulatory authorities. The data set was presented for the first time as late-breaking data during the virtual 25th European Hematology Association (EHA) Annual Congress today (abstract #LB2601).

Additional data presented at EHA includes research from venetoclax in patients who are previously untreated and patients with BIRC3-mutated relapsed/refractory (R/R) CLL, highlighting the medicines broad potential and utility across difficult to treat blood cancers.

The Phase III CLL14 trial evaluated the combination of fixed duration venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab, a commonly used chemoimmunotherapy, in previously untreated CLL patients off treatment for at least 2 years. At Year 3, data confirmed sustained progression free survival (PFS) of the venetoclax combination versus chemoimmunotherapy. The estimated PFS rate for the venetoclax combination (n=216) was 81.9% compared with 49.5% for patients on chemoimmunotherapy (n=216) (median not reached vs 35.6 months; HR = 0.31 [CI: 0.22–0.44]; P<0.001).2

In addition, subgroup analyses from the Phase III MURANO trial, evaluating BIRC3-mutated R/R CLL patients treated with a fixed duration of venetoclax plus rituximab, reported PFS (primary endpoint) and undetectable minimal residual disease (uMRD) responses (secondary endpoint) based on the 4-year follow-up. The analyses found that there was no PFS reduction observed, and nearly half of the patients were able to achieve and maintain uMRD (HR = 1.5 [95% CI: 0.5–4.3; P=0.44 adjusted for TP53, 17pdel and IGHV status).3 This analysis supports the use of time-limited, chemotherapy-free venetoclax plus rituximab in R/R CLL patients with BIRC3 mutations.

The safety profiles in both studies were consistent with previous results.8

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.

-End-

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 uk_pvvendor@abbvie.com.

AbbVie UK Media:

Rupal Antoniou

+44 (0)7870 678 084

Rupal.Antoniou@abbvie.com

Ben Lewry

+44 020 3900 6075

Ben.Lewry@virgohealth.com 

Notes to editors:

About the VIALE-A (M15-656) Phase III trial

A total of 443 treatment-naïve, intensive chemotherapy ineligible AML patients were randomised in this double-blind, placebo-controlled Phase III VIALE-A trial. The trial was designed to evaluate the efficacy and safety of venetoclax in combination with azacitidine (n = 286) compared with placebo in combination with azacitidine (n = 145).1,9

The study met its primary endpoints of statistically significant improvement of overall survival (OS) and composite complete remission rate (CR + CRi). OS and CR + CRi were co-primary endpoints in China, Japan, the European Union (EU) and EU reference countries.1

The study also met secondary endpoints with the venetoclax combination arm resulting in a CR rate of 36.7%, a CR with partial haematological recovery (CRh) rate of 64.7% and a CR + CRi of 66.4%, compared with 17.9% CR, 22.8% CRh and 28.3% CR + CRi in the placebo arm.1

The most common (occurring in >10% of patients) Grade 3/4 adverse events in patients receiving venetoclax plus azacitidine were thrombocytopenia (45%), neutropenia (42%), febrile neutropenia (42%), anaemia (26%), leukopenia (21%), pneumonia (20%) and hypokalaemia (11%).1

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.9 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 2018, the European Commission approved venetoclax plus rituximab for the treatment of patients with relapsed or refractory (R/R) CLL.8 Venetoclax monotherapy was previously approved in the EU for 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. It was approved for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.8

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

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, the AbbVie 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. DiNardo CD, Jonas BA, Pullakart V, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Venetoclax With Azacitidine Vs. Azacitidine In Treatment-Naïve Patients with Acute Myeloid Leukemia Ineligible For Intensive Therapy: The Phase 3 VIALE-A Trial [online]. Poster presented at the virtual 25th European Hemotology Association (EHA) Annual Conference; 11–21 June 2020. Available from: https://library.ehaweb.org/eha/2020/eha25th/303390/courtney.dinardo.a.randomized.double-blind.placebocontrolled.study.of.htmlf=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D1766%2Aces_id%3D27014%2Amarker%3D794%2Afeatured%3D16775 [Last accessed: June 2020].

2. 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. Presented at the 25th EHA Annual Congress; 11–21 June 2020.

3. Kater A P, Wu J, Wang J, et al. Extended Follow-Up in BIRC3-Mutated Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Patients Treated With Fixed-Duration Venetoclax Plus Rituximab: Subgroup Analyses of the MURANO Trial. Presented at the virtual 25th EHA Annual Congress; 11–21 June 2020.

4. Puty, T.C., Sarraf, J.S., Do Carmo Almeida, T.C. et al. Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol. Syst Rev 8, 109 (2019).

5. Cancer Research UK. Acute myeloid leukaemia (AML) statistics. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-aml#heading-Zero [Last accessed: June 2020].

6. Pettit K, Odenike O. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies. Front Oncol. 2015;5:250.

7. National Cancer Institute (2018). Acute Myeloid Leukemia – SEER Stat Fact Sheets. Available from: https://seer.cancer.gov/statfacts/html/amyl.html[Last accessed: June 2020].

8. AbbVie Deutschland GmbH & Co. KG. Venclyxto® (venetoclax): Summary of Product Characteristics [online] 21 April 2020. Available from: https://www.medicines.org.uk/emc/medicine/32650 [Last accessed: June 2020].

9. ClinicalTrials.gov. NCT02993523. A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy [online] 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT02993523 [Last accessed: June 2020].

About Us

We're a company that takes on the toughest health challenges.AbbVie is a global, research-driven 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 us on twitter: @abbvieuk.

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