New long-term data confirm Roche's Gazyva/Gazyvaro extends the lives of people with chronic lymphocytic leukaemia compared to MabThera/Rituxan

• After a follow-up time of nearly five years the CLL11 study shows a 51% reduction in the risk of disease progression or death with Gazyva/Gazyvaro compared to MabThera/Rituxan
• The final analysis reports a clinically meaningful overall survival benefit is seen for Gazyva/Gazyvaro compared to MabThera/Rituxan when combined with chlorambucil
• These data highlight the superiority of Gazyva/Gazyvaro-based treatment over MabThera/Rituxan-based treatment for patients with previously untreated CLL with comorbidities

Basel, 15 June 2018 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced data from the final analysis of the CLL11 study evaluating Gazyva®/Gazyvaro® (obinutuzumab)-based treatment in previously untreated chronic lymphocytic leukaemia (CLL) which will be presented during the Presidential Symposium at the 23rd European Hematology Association (EHA) Annual Congress, 14 - 17 June, in Stockholm. After a follow-up of nearly five years, final results showed clinically meaningful improvements with Gazyva/Gazyvaro plus chlorambucil across multiple endpoints, including progression-free survival (PFS) and overall survival (OS), when compared head-to-head with MabThera®/Rituxan® (rituximab) plus chlorambucil. Gazyva/Gazyvaro-based treatment reduced the risk of death by 24% compared to MabThera/Rituxan-based treatment (median OS not reached vs. 73.1 months, HR= 0.76; 95% CI 0.60-0.97; p<0.0245). These new data add to the growing body of evidence for the OS benefit with Gazyva/Gazyvaro in first-line CLL after the previously reported OS benefit with Gazyva/Gazyvaro combined with chlorambucil versus chlorambucil alone.

"We are very pleased that the majority of patients treated with Gazyva/Gazyvaro are still alive after nearly five years of follow-up in the CLL11 study," said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. "This meaningful survival benefit compared to MabThera/Rituxan-based therapy reinforces that Gazyva/Gazyvaro-based therapy is an important option for people with previously untreated CLL."

After a median observation time of nearly five years (59.4 months) this final analysis of the CLL11 study demonstrated:

• A reduction in the risk of disease progression or death of 51% for patients treated with Gazyva/Gazyvaro plus chlorambucil versus those treated with MabThera/Rituxan plus chlorambucil (median PFS 28.9 vs. 15.7 months, HR= 0.49; 95% CI 0.41-0.58; p<0.0001).
• A clinically meaningful improvement in OS for patients receiving Gazyva/Gazyvaro plus chlorambucil compared to MabThera/Rituxan plus chlorambucil. At the time of final analysis the median OS in the Gazyva/Gazyvaro plus chlorambucil arm was not yet reached which means that more than half of these patients were still alive after nearly five years. A 24% reduction in the risk of death was observed with Gazyva/Gazyvaro plus chlorambucil treatment (median OS not reached vs. 73.1 months, HR= 0.76; 95% CI 0.60-0.97; p<0.0245).
• A prolonged time to initiation of the next therapy (time to new treatment; TTNT) with Gazyva/Gazyvaro plus chlorambucil (median 56.4 vs. 34.9 months, Gazyva/Gazyvaro plus chlorambucil vs. MabThera/Rituxan plus chlorambucil, HR= 0.58; 95% CI 0.46-0.73; p<0.0001).
• Patients treated with Gazyva/Gazyvaro plus chlorambucil achieved a higher rate of minimal residual disease (MRD) negativity versus those treated with MabThera/Rituxan plus chlorambucil (24% vs. 2% of patients MRD-negative, Gazyva/Gazyvaro plus chlorambucil vs. MabThera/Rituxan plus chlorambucil). Being MRD negative means no cancer can be detected in the blood and or bone marrow using a sensitive test.
• No new or unexpected safety concerns for the combination of Gazyva/Gazyvaro plus chlorambucil.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil, for people with previously untreated CLL, based on previously reported data from the CLL11 study.^[1]

About the CLL11 study
CLL11 is a phase III, multicenter, open-label, randomised three-arm study to investigate the safety and efficacy profile of Gazyva/Gazyvaro plus chlorambucil compared to MabThera/Rituxan plus chlorambucil or chlorambucil alone in nearly 800 people with previously untreated CLL and comorbidities. The primary endpoint of the study is PFS with secondary endpoints including response rate, molecular remission rate, OS, TTNT and safety profile. In terms of analysis, the study was divided into three stages:

• Stage 1a compared the addition of Gazyva/Gazyvaro to chlorambucil vs. chlorambucil alone
• Stage 1b compared the addition of MabThera/Rituxan to chlorambucil vs. chlorambucil alone
• Stage 2 compared Gazyva/Gazyvaro plus chlorambucil to MabThera/Rituxan plus chlorambucil

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body's immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL), in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 60 countries in combination with chemotherapy for previously untreated, follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world. ^[2]  CLL mainly affects men and the median age at diagnosis is about 70 years.^[3]  Worldwide, the incidence of all leukaemias is estimated to be over 350,000 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.^[4]

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. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row 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] Goede V, et al. Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions. NEJM. 2014;370:1101-1110
[2] Union for International Cancer Control. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines: Chronic lymphocytic leukemia [Internet; cited 2018 May]. Available from: http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf?ua=1
[3] SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia (CLL) [Internet; cited 2018 May]. Available from: http://seer.cancer.gov/statfacts/html/clyl.html
[4] Wendtner CM, et al. Chronic lymphocytic leukemia. Onkopedia guidelines 2012 [Internet; cited 2018 May]. Available from: https://www.onkopedia-guidelines.info/en/onkopedia/guidelines/chronic-lymphocytic-leukemia-cll/@@view/html/index.html

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