Investor Update

Basel, 8 December 2003

Roche's CERA in cancer patients delivers rapid and sustained correction of anaemia at 3 week dosing intervals
Administration once every three weeks offers patients convenience and flexibility

First results from a phase I/II clinical study demonstrated that Roche’s innovative new chemical entity CERA (Continuous Erythropoiesis Receptor Activator) delivers rapid and sustained increases in haemoglobin levels when given once every three weeks to multiple myeloma cancer patients. This ability to administer CERA once every three weeks may offer greater flexibility and convenience in the treatment of many patients with cancer-related anaemia by harmonizing their anaemia treatment with their chemotherapy regimen, which is often administered on an every three week cycle.

These results, presented during the annual meeting of the American Society of Haematology (ASH), add to the growing body of evidence supporting CERA’s promise as the next generation anaemia agent. Phase III studies with CERA in oncology are poised to begin in the US and Europe later next year.

Dr John Glaspy, Professor of Medicine, UCLA, USA, commented, “Many patients receive chemotherapy regimens every three weeks. If the potential to deliver CERA once every three weeks is demonstrated this would offer patients the opportunity to coincide their anaemia management with their chemotherapy cycle. This would be a great convenience to patients and their caregivers, saving them additional travel time.”

CERA is a Continuous Erythropoiesis Receptor Activator. Studies indicate that CERA has a unique activity at the receptor site. It is postulated this is related to its repeated and rapid attachment and dissociation from the receptor involved in triggering erythropoiesis (red blood cell formation) together with an extended serum half life. This results in more potent stimulation of erythropoiesis, both in magnitude and duration, compared to standard epoetins.

“This new data support the recent excellent results with CERA in anaemia patients and should provide cancer patients with the opportunity of anaemia management that matches their cancer treatment schedules,” according to John Michailidis, Business Director, Roche. “The anaemia market in oncology, particularly in the US, is growing rapidly and this new data will help us with the global commercialization of CERA in this important indication.”

About the study
Results presented at the ASH congress were from an open-label, exploratory, multi-centre, two stage, dose-escalation study to investigate the hemoglobin dose-response, pharmacokinetic and safety profile of CERA in patients with multiple myeloma-related anaemia receiving chemotherapy. Patients received CERA initially for 6 weeks with an option of an additional treatment period of up to 12 weeks. CERA was administered subcutaneously once every 3 weeks.

In stage I 26 patients were randomly assigned to receive: CERA 2.0 µg/kg (n=9), 3.5 µg/kg (n=8) or 5.0 µg/kg (n=9). Following completion of stage I, stage II was initiated with additional patients receiving CERA doses selected based on efficacy and safety data from stage I.
In stage II 38 patients were randomly assigned to receive: CERA 1.0 µg/kg (n=10), 4.2 µg/kg (n=10), 6.5 µg/kg (n=10) or 8.0 µg/kg (n=8) in a sequential manner. The main evaluation was the change in haemoglobin level from baseline to End Of Initial Treatment (EOIT).

Results demonstrated a dose-dependent hemoglobin response to CERA 1.0–4.2 µg/kg. CERA 3.5–8.0 µg/kg produced a mean increase in hemoglobin after 6 weeks of approximately 1.8 g/dL and around 60% of patients had a dose response of >=2 g/dL. These elevated Hb levels were maintained or improved further during the 12 week extension period. CERA demonstrated a favourable safety profile across all treatment groups.

Phase II clinical study results with CERA in the renal setting were presented last month at the American Society of Nephrology Congress, San Diego, USA. CERA effectively increased haemoglobin at all studied doses, with increasing doses providing a more rapid response and extended dosing intervals not influencing the magnitude of the response.

Roche in anaemia
NeoRecormon (epoetin beta) is Roche’s leading anaemia therapy for patients with kidney disease and cancer and it has been marketed for 12 years. In the renal segment, NeoRecormon is the European market leader. NeoRecormon also plays an increasingly important role in the management of anaemia in cancer patients. CERA is the most recent demonstration of Roche’s commitment to anaemia management.

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, 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.

References:
1. Henry D et al. CERA (Continuous Erythropoiesis Receptor Activator) produces a dose-related response in patients with multiple myeloma: an exploratory phase I/II dose escalation study. Poster, American Society of Hematology (ASH) 6-9 December in San Diego, USA1

End of Initial Treatment (EOIT), defined as completion of the core study period, transfusion or dose change.