• Approval is based on randomised phase III MURANO study showing that fixed duration of treatment with Venclyxto plus MabThera is well tolerated and reduced risk of disease progression or death by 83% compared to a current standard of care
  • New combination provides a chemotherapy-free option for treating people with chronic lymphocytic leukaemia whose disease has returned after previous treatment

Basel, 1 November 2018 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission has approved Venclyxto® (venetoclax) in combination with MabThera® (rituximab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy.

"There are approximately 30,000 people living with chronic lymphocytic leukaemia in Europe, an incurable blood cancer that becomes harder to treat with each relapse," said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. "We are pleased that, thanks to this approval, Venclyxto plus MabThera will provide a new chemotherapy-free option for people with previously treated chronic lymphocytic leukaemia, helping them to live longer without their disease progressing compared to a standard-of-care therapy."

This approval is based on results from the randomised phase III MURANO study which showed that a fixed duration of treatment with Venclyxto plus MabThera significantly reduced the risk of disease progression or death (progression-free survival [PFS] as assessed by investigators [INV], primary endpoint of the study) by 83% compared with bendamustine plus MabThera (BR), a current standard of care (HR=0.17; 95% CI 0.11-0.25; p<0.0001). PFS assessed by independent review committee was consistent. In addition, minimal residual disease (MRD)-negativity in peripheral blood at the end of combination treatment was 62.4% with Venclyxto plus MabThera compared to 13.3% with BR. Being MRD-negative means no cancer can be detected in the blood and or bone marrow using a sensitive test. In Europe, MRD is used as an indicator of a patient achieving longer endpoints such as PFS and overall survival. The most commonly observed side effects of Venclyxto plus MabThera included low white blood cell count (neutropenia), diarrhoea and upper respiratory tract infection.

Venclyxto was previously granted conditional marketing authorisation in the EU in December 2016 as a single agent for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor. Today's EU approval follows the US Food and Drug Administration approval in June 2018 of Venclexta® in combination with Rituxan® for the treatment of people with CLL or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. Additional submissions of the MURANO data to health authorities around the world are ongoing.

Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States, under the brand name Venclexta, and commercialised by AbbVie outside of the United States.

About the MURANO Study
MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of fixed duration Venclexta/Venclyxto (venetoclax) in combination with MabThera/Rituxan (rituximab) compared to standard of care bendamustine in combination with MabThera/Rituxan (BR) in patients with relapsed or refractory chronic lymphocytic leukaemia (CLL). Patients on the Venclexta/Venclyxto plus MabThera/Rituxan arm received six cycles of Venclexta/Venclyxto plus MabThera/Rituxan followed by Venclexta/Venclyxto monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with CLL who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta/Venclyxto plus MabThera/Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS) as assessed by investigator (INV). Secondary endpoints included overall survival (OS), overall response rate (ORR), complete response rate (with or without complete blood count recovery, CR/CRi), minimal residual disease (MRD) and safety.

MURANO Study Results *
Treatment arm Venclexta/Venclyxto + MabThera/Rituxan
(n=194)
Bendamustine +
MabThera/Rituxan
(n=195)
PFS (primary endpoint as assessed by INV)
Median PFS Not reached (NR) 17.0 months
Number of events 32 (16.5%) 114 (58.5%)
Hazard Ratio 0.17 (95% CI 0.11-0.25), p<0.0001
Secondary endpoints (as assessed by INV)
ORR 93.3% 67.7%
CR/CRi 26.8% 8.2%
MRD negativity rate at end of combination treatment
Peripheral blood 62.4% 13.3%
Bone marrow 15.5% 1.0%
OS
Number of events 15 27
Hazard ratio 0.48 (95% CI 0.25-0.90), p<0.0001

                   *Data at median follow-up of 24 months

The most common adverse reactions (>=20%) of any grade in patients receiving Venclyxto in the combination study with MabThera were neutropenia, diarrhoea, and upper respiratory tract infection. Death occurred in 11% of people who received Venclexta/Venclyxto plus MabThera/Rituxan compared to 16% for BR.

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the United States, Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory chronic lymphocytic leukaemia (CLL); as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

Venclexta/Venclyxto is approved in more than 50 countries. Roche and AbbVie are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world. [1]
CLL mainly affects men and the median age at diagnosis is about 70 years. [2] In Europe, the incidence of all leukaemias is estimated to be almost 95,000 [3] and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.[1]

About Roche in haematology
For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera/Rituxan (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), and Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Roche's pipeline of investigational haematology medicines includes Tecentriq® (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche's dedication to developing novel molecules in haematology expands beyond malignancy, with the development of Hemlibra® (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare - a strategy that aims to fit the right treatment to each patient in the best way possible. Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the tenth consecutive year, Roche has been recognised as the most sustainable company in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.


References
[1] Wendtner CM, et al. Chronic lymphocytic leukemia. Onkopedia guidelines 2012 [Internet; cited 2018]. Available from: https://www.onkopedia-guidelines.info/en/onkopedia/guidelines/chronic-lymphocytic-leukemia-cll/@@view/html/index.html
[2] SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia (CLL) [Internet; cited 2018]. Available from: http://seer.cancer.gov/statfacts/html/clyl.html.
[3] Calculation for Europe:World Health Organization. GLOBOCAN 2012. [Internet; cited 2018]. Available from: http://gco.iarc.fr/today/fact-sheets-populations



Roche Group Media Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche-global.com
- Nicolas Dunant (Head)
- Patrick Barth
- Ulrike Engels-Lange
- Simone Oeschger
- Anja von Treskow

Attachment