Media Release Basel, 17 November 2012 Roche study showed that Avastin helped people with newly diagnosed glioblastoma live longer without their disease worsening when added to radiation and chemotherapy Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the positive phase III AVAglio study. The study showed Avastin (bevacizumab) in combination with radiation and temozolomide chemotherapy reduced the risk of cancer worsening or death (progression-free survival; PFS) by 36 percent compared to radiation and temozolomide chemotherapy plus placebo (HR=0.64; p<0.0001) in people with newly diagnosed glioblastoma, the most common and aggressive form of primary brain cancer. PFS assessed by trial investigators was a co-primary endpoint for the study. The interim results for overall survival (OS), the other co-primary endpoint, did not reach statistical significance (HR=0.89; p=0.2135). Final data on overall survival are expected in 2013. The data were presented at the 17th Annual Meeting of the Society for Neuro-Oncology in Washington D.C., USA. No new safety findings were observed in the AVAglio study and adverse events were consistent with those seen in previous trials of Avastin across tumour types for approved indications. People with newly diagnosed glioblastoma have few treatment options and need new medicines, said Hal Barron M.D., chief medical officer and head of Global Product Development. An important outcome from the AVAglio study was that patients who received Avastin plus radiation and chemotherapy lived significantly longer without their disease getting worse, and we plan to discuss these data with regulatory authorities. Avastin is currently approved in the United States and almost 40 countries worldwide for the treatment of glioblastoma as a single agent and in some countries in combination with irinotecan for adult patients with progressive disease following prior therapy (recurrent setting). The approval in the USA was granted under the Food and Drug Administration s (FDA) accelerated approval programme. F. Hoffmann-La Roche Ltd 4070 Basel Switzerland Group Communications Roche Group Media Relations Tel. +41 61 688 88 88 Fax +41 61 688 27 75 www.roche.com 1/5
The results of the phase III AVAglio trial were presented in Plenary Session 5 by Professor Olivier Chinot, AVAglio Principal Investigator, President of Association des Neuro-Oncologue d'expression Française (ANOEF), Head of the Neuro-Oncology Department, University Hospital Timone, Marseille, France (Abstract OT-03, Saturday 17 November, 10:45 a.m. Eastern Time). AVAglio study results Primary endpoints: The 36 percent reduction in the risk of disease worsening or death can also be referred to as a 56 percent improvement in PFS (HR=0.64; p<0.0001). A 4.4 month improvement in median PFS was observed when people with newly diagnosed glioblastoma received Avastin in combination with radiation and chemotherapy compared to those who received radiation and chemotherapy plus placebo (10.6 months vs. 6.2 months, respectively, p<0.0001). Interim results for overall survival did not reach statistical significance (HR=0.89; p=0.2135). Final data on OS are expected in 2013. Secondary endpoints: An independent review committee assessment of PFS showed a 39 percent reduction in the risk of disease worsening or death, which can also be referred to as a 64 percent improvement in PFS (HR=0.61; p<0.0001). This was consistent with the magnitude of benefit assessed by the trial investigators. The one-year survival rate was 66 percent for the placebo arm versus 72 percent in the Avastin arm (p = 0.052). The study also showed that during the progression free time patients were able to maintain both their functional independence and a number of relevant health-related quality of life measures, emphasising the importance of extending the PFS time for patients. An additional benefit was that patients in the Avastin arm required less corticosteroids as a result of the extended PFS time. About the AVAglio study AVAglio is a phase III, randomised, double blind, placebo controlled trial that assessed the efficacy and safety profile of Avastin in combination with radiation and temozolomide chemotherapy following surgery or biopsy in patients with newly diagnosed glioblastoma. Patients were randomised to receive either: Avastin plus radiation and temozolomide chemotherapy for six weeks followed by a four-week break. Patients then received Avastin and temozolomide for up to six cycles, followed by Avastin alone until disease progression. 2/5
Radiation, temozolomide and placebo for six weeks followed by a four-week break. Patients then received temozolomide and placebo for up to six cycles, followed by placebo until disease progression. The co-primary endpoints of the study were overall survival and progression free survival as assessed by trial investigators. Secondary endpoints included PFS as assessed by an independent review committee, one- and two-year survival rates, health-related quality of life measures and safety profile. By meeting its co-primary endpoint of progressions free-survival, AVAglio is the first positive phase III study in newly diagnosed glioblastoma since 2005. About glioblastoma Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumour (a tumour that originates in the brain), accounting for approximately one third of all cases diagnosed 1. Glioblastoma (or glioblastoma multiforme; GBM) is the most common and the most aggressive type of glioma 1. Globally, the incidence of GBM is approximately 3 to 4 in 100,000 people annually 2, which means that an estimated 240,000 people worldwide get diagnosed with GBM every year. Glioblastoma is a rational therapeutic target for Avastin as these tumours have among the highest levels of vascular endothelial growth factor (VEGF) of any solid tumour. About Avastin: Over 8 Years of Transforming Cancer Care With the initial approval in the USA for advanced colorectal cancer in 2004, Avastin became the first antiangiogenic therapy made widely available for the treatment of patients with an advanced cancer. Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer and ovarian cancer, and is available in the USA for the treatment of colorectal cancer, non-small cell lung cancer and kidney cancer. In addition, Avastin is approved in the USA and almost 40 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer and breast cancer. Avastin is the only anti-angiogenic therapy available for the treatment of these numerous advanced cancer types, which collectively cause over 2.5 million deaths each year. Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today over one million 3/5
patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types. About Avastin: Mode of Action An independent blood supply is critical for a tumour to grow beyond a certain size (2mm) and spread (metastasise) to other parts of the body. Tumours develop their own blood supply in a process called angiogenesis by releasing vascular endothelial growth factor (VEGF) a key driver for tumour growth. Avastin is an antibody that precisely targets and inhibits VEGF for continuous tumour control. Avastin s precise VEGF inhibition allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments with limited additional impact on the side effects of these therapies. About Roche Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com. All trademarks used or mentioned in this release are protected by law. Additional information - Roche in Oncology: www.roche.com/media/media_backgrounder/media_oncology.htm Roche Group Media Relations Phone: +41-61 688 8888 / e-mail: basel.mediaoffice@roche.com - Alexander Klauser (Head) - Silvia Dobry 4/5
- Daniel Grotzky - Štěpán Kráčala References 1.Central Brain Tumor Registry of the United States (CBTRUS) 2012. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004 2008 (Revised March 23, 2012). http://www.cbtrus.org/reports/reports.html. Last accessed 1 August 2012. 2. Parkin DM, Whelan SL, Ferlay J, et al. Cancer Incidence in Five Continents. Vol. VIII. Lyon, France: International Agency for Research on Cancer Scientific Publications No. 155, 2002. 5/5