Basel, 30 November 2004

Unique cancer drug Avastin now shown to improve survival across different metastatic colorectal cancer regimens

Roche and Genentech, Inc., announced today that Avastin (bevacizumab, rhuMAb-VEGF), a new innovative anti-angiogenesis drug, has shown for the first time that it significantly increases survival in patients with metastatic colorectal cancer when used in combination with a standard oxaliplatin-containing chemotherapy regimen. These patients had previously failed one chemotherapy regimen for their advanced disease.

Preliminary results have shown the study has achieved its primary endpoint showing that patients who received Avastin plus chemotherapy lived nearly two months longer, on average, compared to those who received chemotherapy alone (12.5 months vs 10.7 months). Patients receiving Avastin plus chemotherapy had a 26 percent reduction in the risk of death (hazard ratio of 0.74). Oxaliplatin-containing chemotherapy regimens are widely used in first- and second-line metastatic colorectal cancer therapy.

Colorectal cancer is the third most commonly reported cancer, with 945,000 new cases annually worldwide. It is estimated that more than 50% of people diagnosed with colorectal cancer will die of the disease.¹

“We are delighted with this news,” said William M. Burns, Head of Roche Pharmaceuticals Division. “This is the first time that data have demonstrated the significant survival benefit that Avastin can also bring to patients whose disease progresses after initial anti-tumor treatment. Today’s data highlight the potential of Avastin for many patients with metastatic colorectal cancer, as it has now shown survival benefit when used in either first- or second-line.”

The randomised, controlled, multi-center Phase III study, sponsored by the National Cancer Institute, part of the National Institutes of Health, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG), is the first large-scale study to evaluate Avastin in combination with an oxaliplatin-containing chemotherapy regimen (FOLFOX4)*. It is also the first large-scale study in patients with metastatic colorectal cancer who had failed a previous chemotherapy regimen (relapsed). A total of 829 patients were enrolled in this trial and were randomised to receive treatment with FOLFOX4 with or without Avastin. According to ECOG, preliminary study results will be presented during the ASCO Gastrointestinal Cancers Symposium, January 27-29, 2005 in Hollywood, Florida. Trials investigating the use of Avastin with an oxaliplatin-containing regimen as adjuvant (post operation) treatment and first-line treatment for patients with metastatic colorectal cancer are currently ongoing.

“These trial results are immensely important because they provide striking evidence that Avastin can be safely combined with the many different chemotherapy regimens commonly used in the treatment of advanced colorectal cancer,” commented Stefan M. Manth, Head of Roche Oncology.

Avastin received fast-track approval by the US Food and Drug Administration (FDA) and was launched in the US in February 2004. In October 2004, Roche received a positive recommendation from the European Committee for Medicinal Products for Human Use (CHMP) for Avastin for first-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil (5-FU)/folinic acid or intravenous 5-FU/folinic acid/irinotecan. Avastin will now be proposed for final marketing approval by the European Commission.

Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in advanced colorectal cancer with other chemotherapies and also expanding into the adjuvant setting. As Avastin’s mechanism may be relevant in a number of malignant tumours, Roche and Genentech are also investigating the potential clinical benefit of Avastin in other cancers, including non-small cell lung cancer, pancreatic cancer, renal cell carcinoma and others. Approximately 15,000 patients are expected to be enrolled into clinical trials over the next years worldwide.

About Avastin
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).

Earlier this year, the New England Journal of Medicine published results of a pivotal Phase III study which demonstrated that the addition of Avastin to standard IFL chemotherapy (irinotecan/5-FU/leucovorin) significantly extends survival in patients with previously untreated advanced colorectal cancer. The study, in which more than 900 patients participated, showed that Avastin plus chemotherapy increased overall survival by nearly five months (20.3 months vs 15.6 months) compared to chemotherapy alone.²

Roche in Oncology
Within the last five years the Roche Group, including its members Genentech in the United States and Chugai in Japan, has become the world’s leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented five products with survival benefit in different major tumour indications: Xeloda and Herceptin in advanced stage breast cancer, MabThera in non-Hodgkin’s lymphoma, Avastin in colorectal carcinoma and Tarceva in non-small cell lung cancer and pancreatic carcinoma.

In the United States Herceptin, MabThera, Avastin and Tarceva are marketed either by Genentech alone or together with its partners Biogen Idec Inc. (MabThera) and OSI (Tarceva). Outside of the United States, Roche and its Japanese partner Chugai are responsible for the marketing of these medicines.

The Roche oncology portfolio also includes NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcaemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (hairy cell and chronic myeloid leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of Roche’s commitment to anaemia management. The Roche Group’s cancer medicines generated sales of more than 5.6 billion Swiss francs in the first nine months of 2004.

In addition to the medicines, Roche is developing new diagnostic tests that will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumour markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, Roche will continue to be the leader in providing cancer-focused treatments and diagnostics.

Roche has four research sites (two in the United States and one each in Germany and Japan) and five development sites (two in the United States and one each in UK, Australia and Switzerland).

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is one of the world’s leading companies in the global diagnostics market, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

All trademarks used or mentioned in this release are legally protected.

Notes to Editor:
* FOLFOX4 is a standard chemotherapy combination with oxaliplatin, 5-fluorouracil and leucovorin.

Further information:
- Gnenetech: www.gene.com
- Cancer: www.health-kiosk.ch

References:
1 J. Ferlay, F. Bray, P. Pisani and D.M. Parkin. GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC CancerBase No. 5. Lyon, IARCPress, 2001
2 Hurwitz, H, Fehrenbacher, L, Novotny, W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin
for Metastatic Colorectal Cancer. New England Journal of Medicine 2004; 350(23): 2335–2342