Basel, 13 April 2004

MabThera: Primary endpoints of phase III trial met two years early due to superior efficacy benefits in relapsed indolent non-Hodgkin's lymphoma

Roche has been informed that a phase III study¹ evaluating the use of MabThera (rituximab) in patients with relapsed indolent non-Hodgkin’s lymphoma (NHL) has met its primary endpoints two years earlier than expected.

In the two-part trial, patients were randomly assigned to receive MabThera plus chemotherapy or chemotherapy alone as initial treatment, and responding patients were then randomly assigned to receive MabThera for two years as maintenance therapy, or no further treatment. A pre-planned interim analysis showed that MabThera was the best therapeutic option in both parts of the trial: MabThera plus chemotherapy was significantly more effective than chemotherapy alone as initial treatment, and patients subsequently treated with MabThera maintenance for two years had significantly better progression-free survival than those who received no further treatment.

“More than half of patients with relapsed indolent NHL are currently treated with chemotherapy alone. This large trial confirms that MabThera should be the standard of care for patients with relapsed indolent NHL” said William M. Burns, Head of Roche’s Pharmaceuticals Division. “Moreover, this is the third study in indolent NHL to confirm the benefits of MabThera maintenance treatment. Due to these impressive results more patients will now benefit from MabThera for a longer time.”

The Independent Data Monitoring Committee (IDMC) concluded that the trial met its primary endpoints (response rate and progression-free survival) earlier than planned. The IDMC recommended changing the objective of the trial to answer the question of whether MabThera maintenance therapy is beneficial for patients receiving MabThera plus chemotherapy as initial treatment. The trial in its original design was not powered to answer this question. Therefore, the trial protocol will be amended so that all patients receive MabThera plus chemotherapy as initial treatment, and responding patients then be randomly assigned to receive MabThera as maintenance therapy for two years, or no further treatment.

Non-Hodgkin’s lymphoma affects 1.5 million people worldwide. Indolent NHL, representing about 45% of NHL patients, is a slow developing but serious cancer of the lymphatic system. NHL is one of the fastest growing cancers and has grown in incidence by 80% since the early 1970s.ⁱ

About the study
The international cooperative group phase III trial was conducted in 18 countriesⁱⁱ and recruited patients with relapsed indolent NHL. Patients were randomised to receive either six cycles of MabThera in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, or CHOP chemotherapy alone. Patients who responded to initial treatment were then randomised to prolonged MabThera treatment (maintenance therapy) or no further treatment. MabThera maintenance therapy consisted of one dose of MabThera every three months for two years. In this study, the primary endpoints were response rates and progression-free survival for the initial treatment and maintenance parts of the study, respectively. Progression-free survival was evaluated as the time from randomisation to disease progression or death.

About MabThera
MabThera is a therapeutic antibody that binds to a particular protein - the CD20 antigen - on the surface of normal and malignant B-cells. It then recruits the body's natural defences to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

MabThera is indicated as a single-agent treatment for relapsed or refractory indolent NHL, and received European approval in March 2002 for the treatment of aggressive NHL in combination with CHOP chemotherapy. MabThera is known as Rituxan in the United States, Japan and Canada. More than 370,000 patients have been treated with MabThera worldwide to date.

Genentech and Biogen Idec co-market MabThera in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

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 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). Roche’s cancer medicines generated sales of more than 6 billion Swiss francs in 2003.

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 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 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.

¹ European Organization for Research and Treatment of Cancer (EORTC) 20981

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

Notes to editors:
ⁱ World Health Report 2000, World Health Organization, www.who.int.
ⁱⁱ Countries that participated in the study: Canada, Australia, The Netherlands, The UK, Norway, Slovenia, Slovakia, Belgium, Hungary, South Africa, Sweden, New Zealand, Denmark, Egypt, France, Switzerland, Italy, Poland.

Further Information:

• The Lymphoma Coalition
• “Cancer- uncontrolled cell proliferation”
• World Health Organization