Media Release

Basel, 27. March 2007

Roche submits application to the FDA for use of XELOX (Xeloda plus oxaliplatin) with or without Avastin for the treatment of advanced colorectal cancer
Submission based on results from trials showing XELOX is as effective as standard of care in terms of progression-free survival


Roche announced today the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for the use of Xeloda (capecitabine) in combination with oxaliplatin – XELOX – with or without Avastin (bevacizumab) in the treatment of metastatic colorectal cancer.

"This filing marks a significant milestone for Xeloda, which continues to demonstrate its value as a cornerstone in combination therapies, as in this case with oxaliplatin and Avastin. It further supports Roche’s longstanding commitment to advancing treatment for patients with colorectal cancer," said Jean-Jacques Garaud, Roche’s Global Head Pharma Development.

The submission to the FDA is based on results from two large, international, Phase III studies (NO16966 and NO16967) which showed XELOX to be as effective - in terms of progression-free survival (PFS) - as the current standard treatment, FOLFOX- 4 (intravenous bolus and infusional 5-fluorouracil plus oxaliplatin). Study NO16966 also showed that XELOX in combination with Avastin significantly improved progression-free survival over XELOX alone.

In Europe, Roche will be applying for a label extension for Xeloda use in combinations, including with oxaliplatin (XELOX) and Avastin, for the treatment of metastatic (advanced) colorectal cancer. Similarly, the label extension for Avastin broadens the use of the treatment to include combination with fluoropyrimidine- based chemotherapy in patients with metastatic cancer of the colon or rectum.

Colorectal cancer accounts for 13 percent of all cancers in Europe.¹

Avastin was first approved, in Europe, in January 2005 for first-line treatment of patients with advanced colorectal cancer in combination with chemotherapy regimens of intravenous
5-fluorouracil (i.v. 5-FU)/folinic acid or i.v. 5FU/folinic acid/irinotecan. Xeloda is currently indicated as monotherapy for first-line treatment of patients with advanced colorectal cancer. Xeloda is also indicated as post-surgery treatment for colon cancer.

About the Studies

NO16966
NO16966 is a large, international Phase III trial which finally recruited 2,034 patients. It was originally planned to compare XELOX vs FOLFOX as first-line treatment in metastatic colorectal cancer.

After release of the pivotal Avastin data in colorectal cancer in 2003, the protocol was amended to investigate using a 2 by 2 factorial design:

• FOLFOX/XELOX + placebo vs FOLFOX/XELOX + Avastin

The primary objective was to answer two questions: 1) whether the XELOX regimen is non-inferior to FOLFOX; 2) whether the addition of Avastin to chemotherapy improved progression-free survival compared to chemotherapy alone. The secondary endpoints included overall survival, overall response rates, time to, and duration of, response and safety profile.

Results of the study showed:

• The chemotherapy combination XELOX is as effective in terms of progression-free survival- a measure of the time patients live without their disease progressing - as FOLFOX;
• The addition of Avastin to chemotherapy (FOLFOX and XELOX) significantly improved progression-free survival compared to chemotherapy alone.

NO16967
The NO16967 trial is a large, international phase III trial which randomized 627 patients from 15 countries world-wide who had previously received chemotherapy and whose disease had returned or continued to progress.
The primary objective was to answer whether the XELOX regimen (Xeloda plus oxaliplatin) is as effective as FOLFOX-4 (i.v. bolus and infusional 5-FU/leucovorin plus oxaliplatin) in terms of progression free-survival. The secondary outcomes to be reviewed included overall survival, overall response rates, and safety profile.

The results showed:

• The chemotherapy combination XELOX is as effective in delaying disease progression as the chemotherapy combination FOLFOX.

About Xeloda (capecitabine)
Xeloda is licensed in more than 90 countries worldwide including the EU, USA, Japan, Australia and Canada and has been shown to be an effective, safe, simple and convenient oral chemotherapy in treating over 1 million patients to date.

Roche received marketing authorisation for Xeloda as a first-line monotherapy (by itself) in the treatment of metastatic colorectal cancer (colorectal cancer that has spread to other parts of the body) in most countries (including the EU and USA) in 2001. Xeloda has also been approved by the European Medicines Agency (EMEA) and U.S. Food and Drug Administration (FDA) for adjuvant (post-surgery) treatment of colon cancer in March and June 2005, respectively.

Xeloda is licensed in combination with Taxotere (docetaxel) in women with metastatic breast cancer (breast cancer that has spread to other parts of the body) and whose disease has progressed following i.v. chemotherapy with anthracyclines.

Xeloda monotherapy is also indicated for treatment of patients with metastatic breast cancer that is resistant to other chemotherapy drugs such as paclitaxel and anthracyclines. Xeloda recently received approval in South Korea for the first-line treatment of patients with locally advanced (metastatic) pancreatic cancer, in combination with gemcitabine. Xeloda is licensed in South Korea for the first-line treatment of stomach cancer.

The most commonly reported adverse events with Xeloda include diarrhoea, abdominal pain, nausea, stomatitis and hand-foot syndrome (palmar-plantar erythrodysesthaesia).

About Avastin (bevacizumab)
Avastin is the first treatment that inhibits angiogenesis - the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis).

In the US, Avastin was approved in February 2004 and in Europe in January 2005 for first-line treatment of patients with metastatic colorectal cancer. It received another approval in the US in June 2006 as a second-line treatment for patients with advanced colorectal cancer. Following priority review, Avastin was approved by the FDA in October 2006 for the treatment of non-small cell lung cancer (NSCLC); a filing for the same indication was submitted to EU authorities in August 2006. Most recently (in February 2007), a positive recommendation was received by the CHMP for the use of Avastin in first line treatment of metastatic breast cancer and a positive recommendation was received in Japan for the use of Avastin in patients with advanced or recurrent colorectal cancer.

Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant ie post-operation). The total development programme is expected to include over 40,000 patients worldwide.

For more information, please visit www.avastin-info.com

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at www.roche.com.

All trademarks used or mentioned in this release are protected by law.

Further Information
- Roche in oncology
- Roche: www.roche.com
Broadcast quality B-roll including doctor, caregiver and patient interviews is available for download via www.thenewsmarket.com

References:
1) Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Annals of Oncology 2005;16:481-488