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Investor Update

Basel, 14 December 2007


Avastin and Xeloda receive positive recommendations for label extensions in Europe for treatment of advanced colorectal cancer

Roche has received positive recommendations for the Marketing Authorisation extensions for both its anti-angiogenic agent Avastin (bevacizumab) and oral chemotherapy Xeloda (capecitabine) from the European Committee for Medicinal Products for Human Use (CHMP).  The recommendation for the extended label of Xeloda aims to broaden its use in combination with other chemotherapies for the treatment of advanced colorectal cancer. Similarly, the label extension for Avastin aims to broaden its use to include Avastin with XELOX (Xeloda plus oxaliplatin) or FOLFOX-4 (5-FU/LV plus oxaliplatin) in patients with advanced colorectal cancer (beyond the current label with 5-FU/LV and 5-FU/LV/irinotecan).

The positive recommendations are based on the results of three large international Phase III pivotal studies (NO16966 and NO16967 for Xeloda and NO16966 and E3200 for Avastin).

Regarding Xeloda, studies NO16966 and NO16967 showed:

- XELOX to be at least as effective (non-inferior) – in terms of both progression-free survival (PFS) and overall survival – as a current standard treatment, FOLFOX-4 (intravenous bolus and infusional 5-FU/LV plus oxaliplatin) for both 1st and 2nd line treatment.

Regarding Avastin:

The study NO16966 showed that:

- The addition of Avastin to chemotherapy (XELOX or FOLFOX-4) significantly improved progression-free survival by 20% compared with chemotherapy alone.

- In patients that received treatment until disease progression, the benefit was even greater, and adding Avastin to chemotherapy improved progression-free survival by 58%.

The study E3200 showed that:

- The addition of Avastin to chemotherapy (FOLFOX-4) for patients having relapsed disease improved overall survival by 33% compared to patients who received FOLFOX-4 alone.

“The CHMP positive opinion is encouraging news for patients and healthcare providers in the fight against colorectal cancer,” said Jean-Jacques Garaud, Head of Global Pharma Development at Roche.  “We look forward to receiving EU approval, which will mark another milestone in our commitment to developing effective and safe treatments for the thousands of colorectal cancer patients throughout the world.”

No new safety findings related to Avastin or Xeloda were observed in either trial.  

These filings in Europe followed the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) in March for the use of XELOX (Xeloda in combination with oxaliplatin) with or without Avastin (bevacizumab) in the treatment of advanced colorectal cancer.

Details of 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-4 as first-line treatment in advanced 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-4/XELOX + placebo vs FOLFOX-4/XELOX + Avastin.

The primary objective was to answer two questions: 1) whether the XELOX regimen is non-inferior to FOLFOX-4; 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-4;
  • The addition of Avastin to chemotherapy (FOLFOX-4 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 worldwide who had previously received irinotecan-containing combination 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/LV 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 terms of progression-free survival as the chemotherapy combination FOLFOX-4.

E3200
The E3200 study is a randomized, controlled, multicenter Phase III trial (E3200) of 829 patients with advanced or advanced CRC who had received previous treatment with irinotecan and 5-FU as initial therapy for advanced disease or as adjuvant therapy.  The study showed that patients who received Avastin plus the 5-FU-based chemotherapy regimen known as FOLFOX-4 (oxaliplatin/5-FU/leucovorin) had a 25% reduction in the risk of death (based on a hazard ratio of 0.75), the primary endpoint, which is equivalent to a 33% improvement in overall survival, compared to patients who received FOLFOX-4 alone. Median survival for patients receiving Avastin plus FOLFOX-4 was 12.9 months, compared to 10.8 months for those receiving FOLFOX-4 alone.

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 in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the 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 has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. Additional information is available on the Internet at www.roche.com.