Media Release

Basel, 7 June 2004

Roche at ASCO: Important data underscore Roche’s leading position in oncology
Outstanding study results on Tarceva, Xeloda and MabThera

Roche, in collaboration with Genentech, OSI Pharmaceuticals and Biogen Idec, presented impressive data on its portfolio of cancer drugs during the 40th American Society of Clinical Oncology (ASCO) meeting in New Orleans, USA. Over 100 abstracts and 9 oral presentations covered data in colon/colorectal cancer, breast and lung cancer as well as in Non-Hodgkin’s Lymphoma (NHL): Amongst the data highlights were:

• Tarceva achieves a significant 42.5% improvement in median survival in patients with advanced lung cancer
• Avastin and Tarceva combination yields initial promising results in recurrent NSCLC and metastatic renal cell carcinoma
• Xeloda after surgery significantly increases the number of patients free from colon cancer by 14% compared to intravenous 5-fluorouracil/leucovorin
• MabThera: First-line therapy achieves an impressive 95% survival rate in patients under 60 years with aggressive NHL and maintenance therapy improves progression free survival in patients with indolent NHL
• Herceptin data from several studies confirm the drug’s excellent efficacy in metastatic breast cancer and shows promising results in the treatment of early breast cancer

William M. Burns, Head of Roche’s Pharmaceuticals Division said:” This impressive volume of convincing data demonstrates our strength in developing innovative cancer treatments. New breakthrough drugs like Tarceva and Avastin represent further milestones in cancer treatment and will give new hope to cancer patients. In addition, our established cancer drugs MabThera, Xeloda and Herceptin, have generated very promising results for additional use in major new indications. Overall our oncology portfolio now consists of five drugs with a proven survival benefit which puts us in an unrivalled position and further underscores Roche’s leadership in oncology.”

Tarceva: first EGFR-targeted anticancer treatment ever to have shown survival benefit in any tumour type
Tarceva (erlotinib) achieved a significant 42.5% improvement in median survival compared to placebo in patients with advanced non-small cell lung cancer (NSCLC). Based on these study results Roche will work with regulatory authorities around the world to make this medicine available to patients with NSCLC as soon as possible. Non-small cell lung cancer is the most common form of the disease and accounts for almost 80 percent of all lung cancer – it has a very high mortality rate and few treatment options exist.

The study, conducted by the Clinical Trials Group of the National Cancer Institute of Canada in collaboration with OSI Pharmaceuticals, involved 731 patients with advanced NSCLC who had failed to respond to first or second line chemotherapy. The study met its primary endpoint in that patients receiving Tarceva lived longer than those in the placebo arm (6.7 months vs 4.7 months)

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, and also met all of its secondary endpoints including improving time to symptomatic deterioration, progression-free survival and response rate. In addition, analysis of the results showed a treatment benefit in all subsets of patients examined.

According to the World Health Organization, there are more than 1.2 million new cases worldwide of lung and bronchial cancer each year, causing approximately 1.1 million deaths annually. Non-small cell lung cancer is the most common form of the disease and accounts for almost 80 percent of all lung cancer.

Xeloda: reduces significantly the risk of tumours coming back after surgery
New data from the X-ACT trial (Xeloda in Adjuvant Colon Cancer Therapy), involving almost 2,000 patients demonstrates that Xeloda (capecitabine), a targeted oral chemotherapy, could replace the current standard therapy known as the Mayo Clinic regimen (intravenous 5-FU/LV) due to its superior efficacy and safety.

The global study successfully met its primary endpoint of demonstrating at least equivalent disease free survival. More remarkably, the study highlights that Xeloda reduces the risk of tumours coming back (relapse-free survival) by an impressive 14% compared to i.v. 5-FU/LV. This means that, each year, if treated with Xeloda, nearly 4,000 additional patients worldwide would not hear the dreaded words “Your cancer has come back.” Roche will submit the study results to global regulatory authorities.

Roche presently supports studies of Xeloda on a global level enrolling over 6,000 patients per year which will further establish the importance of Xeloda in the fight against cancer.

In 2000, colorectal cancer was the third most commonly reported cancer with 945,000 new cases worldwide. It is estimated that over 50% of people diagnosed with colorectal cancer will die of the disease, and it is one of the most common cancers in developed countries

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. Chemotherapy following surgery (adjuvant therapy) is one of the most common treatment approaches in patients diagnosed with the disease.

Avastin: increased survival in colorectal cancer and initial promising results in other tumour types
Results were presented from Phase I/II clinical studies examining the combination of Avastin (bevacizumab, rhuMAb-VEGF) and Tarceva in the treatment of recurrent non-small cell lung cancer (NSCLC) and metastatic renal cell carcinoma (kidney cancer). These trials are important because patients received no chemotherapy and instead were treated with a combination of two therapies targeted at two distinct avenues of growth in cancer: angiogenesis and EGFR signaling.
Investigators presented preliminary results from a single-arm phase II in metastatic renal cell carcinoma

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. At the time of analysis, 58 patients were evaluable for response. The authors reported that at eight weeks, 21% of patients (12/58) experienced an objective response (defined as a 50% or greater decrease in the size of a tumour) to the combined therapy and 66% (38/58) experienced a minor response or disease stabilisation. At six months, 67% of the evaluable patients (38/58) had progression-free survival and after one year, 50% of patients (29/58) had progression-free survival. In a phase I/II study evaluating the combination of Avastin and Tarceva in recurrent non-small cell lung cancer

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, preliminary analysis of 40 patients has shown a median survival of 12.6 months, a median progression-free survival of 7 months and an estimated one-year survival of 54 percent.

Traditionally patients with relapsed NSCLC are treated with chemotherapy, which may be very poorly tolerated by some advanced patients. If randomized, Phase III trials of Avastin plus Tarceva show clinical benefit, this combination could provide an important treatment option that does not include chemotherapy.

Recently, the New England Journal of Medicine published study results that demonstrate the addition of Avastin to standard chemotherapy significantly extends survival in patients with first-line (previously untreated) metastatic colorectal cancer

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. The New England Journal of Medicine publication of the Avastin pivotal study is significant because it is the first published trial of its kind. These data are the first positive results from a Phase III trial of a unique therapy that works by preventing the formation of new blood vessels, a process called angiogenesis. Following FDA approval earlier this year, Roche is working closely with the European regulatory authorities to bring Avastin, the first treatment of its kind, to patients as quickly as possible.

MabThera: impressive survival rate in aggressive NHL and dramatic improvement in progression-free survival in maintenance therapy in indolent NHL
Aggressive NHL: New MabThera data from the MabThera International Trial, (MInT

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) revealed extremely positive survival benefits for younger patients with aggressive NHL. The study showed an overall survival of 95% for those patients who received MabThera (rituximab) in combination with chemotherapy. This compliments the impressive survival benefits previously seen in a study of patients over 60 years old. Based on these data, MabThera plus chemotherapy should become the standard first-line treatment of patients of all ages suffering from this aggressive and life-threatening form of cancer.

In December 2003, the MInT study was halted two years earlier than expected following an interim analysis of the data that revealed that the pre-specified criteria for closing the study were reached early, demonstrated by a statistically significant improvement in time to treatment failure (TTF) in patients receiving MabThera plus chemotherapy.

Indolent NHL: Data from a large, randomised phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG 1496

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) showed that MabThera maintenance therapy for two years following an initial course of chemotherapy resulted in a dramatic improvement in progression-free survival in patients suffering from indolent Non-Hodgkin’s lymphoma (NHL). Almost twice as many patients were free of disease progression compared to those who received no further treatment (73% versus 43%).
This trial paves the way for its use in patients with indolent NHL, who responded well to initial induction therapy. Maintenance treatment with MabThera keeps the disease under control and patients free from disease for an extended period of time.

Mantle Cell Lymphoma (MCL): Other phase III data reveal that previously untreated patients with mantle cell lymphoma, an intermediate grade form of non-Hodgkin’s lymphoma, treated with MabThera plus chemotherapy first-line experienced significantly higher remission rates and prolonged time to treatment failure compared to chemotherapy alone. Mantle cell lymphoma is a disease that typically affects elderly patients and carries a poor prognosis, with a median survival of only three to four years. The study

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, led by Professor W. Hiddemann of the German Low Grade Lymphoma Study Group (GLSG), indicates that MabThera plus chemotherapy is a highly effective first-line therapy in treating MCL.

Non-Hodgkin’s lymphoma affects 1.5 million people worldwide. About 55% of NHL patients have the aggressive form of the disease, which, if left untreated, can be fatal within six months. The remaining 45% suffer from indolent NHL, which is slow developing, but incurable. NHL is one of the fastest growing cancers and has grown in incidence by 80% since the early 1970s.

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Roche in Oncology
Within the last five years the Roche Group has become the world’s leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit: Herceptin, MabThera, Xeloda and Avastin which has been launched by Genentech in the US recently, treat a range of malignancies such as breast cancer, non-Hodgkin’s lymphoma and colorectal cancer. Other key products include NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. Roche’s cancer medicines generated sales of more than 6 billion Swiss francs in 2003.

In a recent phase III study Tarceva met its primary endpoint of improving overall survival in patients with non-small cell lung cancer.

Roche is developing new tests, which will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumor markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, we will continue to be the leaders in providing cancer focused treatments and diagnostics.

Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland).

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of 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 employs roughly 65,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

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

Further information:
- www.asco.org

On Tuesday 8 June a Roche analyst conference will be held at ASCO from 1:30 a.m. to 3 a.m. CET (Central European Time). The briefing will be webcast and presentation slides can be downloaded from ir.roche.com. A replay of the conference will be available on demand at http://ir.roche.com.

1 Shepherd, F.; A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or or 2nd line chemotherapy. A national Cancer Institute of Canada Clinical Trials Group (NCIC). (Abstract #7022), ASCO 2004
2 World Health Organisation. Globocan 2000: Cancer Incidence, Mortality and Prevalence Worldwide. 2000
3 Phase II Study of Tarceva and Avastin in metastatic renal cell carcinoma (Abstract #4502)
4 Phase I/II Study of Avastin and Tarceva in recurrent non-small cell lung cancer (Abstract #2000)
5 Hurwitz H, Fehrenbacher L, Novotny W, et al. Addition of bevacizumab (rhuMab-VEGF) to bolus IFL in the first-line treatment of patients with metastatic colorectal cancer: results of a randomized Phase III trial. New England Journal of Medicine 2004;350(23)
6 Pfreundschuh M et al. Abstract #6500. Randomized intergroup trial of first line treatment for patients <=60 years with diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) with a CHOP-like regiment with or without the anti-CD20 antibody rituximab – early stopping after first interim analysis. Annual Meeting of the American Society of Clinical Oncology (ASCO), June 2004.
7 Hochster H et al. Abstract #6502. Results of E1496: A Phase III Trial of CVP With or Without Maintenance Rituximab in Advanced Indolent Lymphoma (NHL). Annual Meeting of the American Society of Clinical Oncology (ASCO), June 2004.
8 Hiddemann, M et al. Abstract #6501. The addition of Rituximab to front line therapy with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) increases the remission rate and prolongs the time to treatment failure (TTF) significantly over CHOP alone in mantle cell lymphoma (MCL) – Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). Annual Meeting of the American Society of Clinical Oncology (ASCO), June 2004.
9 World Health Report 2000, World Health Organization, www.who.int.