Basel, 17 February 2006

Roche files Herceptin for early-stage HER2-positive breast cancer with European Authorities
Similar license extension for Herceptin recently filed in the US

Roche today announced the submission of a Marketing Authorisation application to the European Medicines Agency (EMEA) for Herceptin (trastuzumab) as adjuvant treatment for early-stage HER2-positive breast cancer. The application is based on data from the international HERA (HERceptin Adjuvant) study which showed that Herceptin following standard chemotherapy significantly reduces the risk of cancer coming back, by an outstanding 46%.¹

HER2-positive breast cancer, which affects approximately 20 – 30% of women with breast cancer,² demands special and immediate attention because HER2-positive tumours are fast growing. Results from four large trials,³ with nearly 12,000 patients analysed from around the globe, provide consistent evidence that Herceptin reduces the risk of cancer coming back by about half, providing the best chance of long-term survival to women with this aggressive form of early-stage breast cancer.

“The outstanding benefits we have seen from Herceptin as post-surgical therapy for early-stage breast cancer underpin the importance of securing patient access to this drug as quickly as possible,” commented Ed Holdener, Head of Roche’s Global Pharma Development. “We are very pleased to have been able to progress this application so rapidly, and commend the medical community and regulatory authorities worldwide for their close collaboration and continued support.”

Genentech similarly filed a supplemental Biologic License Application (sBLA) for the use of Herceptin in early-stage HER2-positive breast cancer with the US Food and Drug Administration (FDA) just two days before the European filing. The application is based on data from a combined interim analysis of two large US trials,⁴ and Genentech has requested a priority review designation.

About the HERA study
HERA, conducted by the Roche and Breast International Group (BIG),⁵ is one of the largest adjuvant studies ever carried out among breast cancer patients; enrolment to the trial began in December 2001, and nearly 5,100 HER2-positive patients were enrolled at 480 sites in 39 countries across the world. HERA is a randomised trial, which, following standard adjuvant systemic chemotherapy and radiotherapy (if applicable), evaluates observation versus Herceptin every three weeks for 12 months or 24 months in women with early-stage HER2-positive breast cancer. The HERA study allowed for the use of a wide range of chemotherapy regimens, and both lymph node-positive and lymph node-negative patients were eligible for entry into the trial.

According to the interim analysis, the primary efficacy endpoint was met, showing that in the 12-month arm, patients who received Herceptin had a statistically significant improvement in disease-free survival (the length of time after treatment during which no disease is found). At a median follow-up of one year, the secondary endpoint of overall survival had not reached statistical significance, but showed a clear trend towards an improvement in overall survival, which is to be confirmed as the data mature.

The interim analysis compared Herceptin versus observation and did not include a comparison of 12 months versus 24 months treatment duration. The trial will continue to assess this comparison and data will become available in due time as the study matures.

The HERA study has an external Independent Data Monitoring Committee (IDMC) that regularly reviews safety data. No safety concerns were raised by the IDMC, and the incidence of congestive heart failure was very low (0.5% in the Herceptin arms vs. 0% in the observation arm). Patients in this study will continue to be followed for any side effects.

About breast cancer and Herceptin
Eight to nine percent of women will develop breast cancer during their lifetime, making it one of the most common types of cancer in women.⁶ Each year more than one million new cases of breast cancer are diagnosed worldwide, with a death rate of nearly 400,000 people per year.

In HER2-positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as ‘HER2 positivity.’ High levels of HER2 are present in a particularly aggressive form of the disease which responds poorly to chemotherapy. Research shows that HER2-positivity affects approximately 20-30% of women with breast cancer.

Herceptin is a humanised antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. In addition to its efficacy in the early-stage breast cancer setting, Herceptin also has demonstrated improved survival in the advanced (metastatic) setting, where its addition to chemotherapy allows patients to live up to one-third longer than chemotherapy alone.⁷

Herceptin received approval in the European Union in 2000 for use in patients with metastatic breast cancer, whose tumours overexpress the HER2 protein. In addition to being indicated for use in combination with docetaxel as a first-line therapy in HER2-positive patients who have not received chemotherapy for their metastatic disease, it is also indicated as a first-line therapy in combination with paclitaxel where anthracyclines are unsuitable, and as a single agent in third-line therapy. Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat over 230,000 HER2-positive breast cancer patients worldwide.

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 a supplier of innovative products and services for the early detection, 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 a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries 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 (www.roche.com).

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


Additional information:
- About Genentech
- Roche in Oncology
- Roche Health Kiosk on cancer
- Video clips - in broadcast standard, free of charge

References:
1 Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. A Randomized Trial of Trastuzumab Following Adjuvant Chemotherapy in Women with HER2 Positive Breast Cancer. New England Journal of Medicine 353:16 2005.
2 Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 9: 75-85, 2002.
3 NCCTG N9831 (US), NSABP B-31 (US), HERA – HERceptin Adjuvant (international), BCIRG 006 (international)
4 Romond, E., Perez, E. et al. Trastuzumab plus Adjuvant Chemotherapy for Operable HER2 Positive Breast Cancer. New England Journal of Medicine 353:16 2005.
5 Collaborative partners for the HERA study include: Roche, BIG and its affiliated collaborative groups, plus non-affiliated collaborative groups, and independent sites.
6 World Health Organization, 2000.
7 Extra JM, Cognetti F, Maraninchi D et al. Long-term survival demonstrated with trastuzumab plus docetaxel: 24-month data from a randomised trial (M77001) in HER2-positive metastatic breast cancer. Abstract #555, American Society for Clinical Oncology (ASCO) Annual Meeting 2005.