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Investor Update

Basel, 3 June 2005

NeoRecormon offers patients maximum anaemia control with minimum injection discomfort compared to Aranesp

Comparative new French data show that subcutaneous injection of NeoRecormon is significantly less painful than Aranesp

New data from a comparative study show that people experience significantly less pain and discomfort when given subcutaneous injections of the anaemia treatment NeoRecormon (epoetin beta) compared to Aranesp (darbepoetin alfa).

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Both treatments (erythropoiesis-stimulating agents (ESAs)) are widely used to treat anaemia in patients suffering from renal disease or cancer. This data are good news as ESAs have to be taken regularly and local pain and discomfort can affect patients’ willingness to continue with treatment.

Commenting on the new data Professor François Berthoux of the CHU Saint Etienne, France and scientific committee member of the study said, “Our findings demonstrated that subcutaneous administration of NeoRecormon causes less pain and discomfort and was better tolerated than Aranesp."

ESAs can either be given via intravenous or subcutaneous injections. Injection into the skin of ESAs has a number of advantages, as it allows individuals to self-administer at their convenience, treatment can therefore continue without the need for clinic visits. In addition, the subcutaneous route of administration is recommended in treatment guidelines for patients with chronic kidney disease (CKD) not undergoing dialysis, for both economic and practical reasons. Subcutaneous NeoRecormon achieves the same therapeutic effect as intravenous administration with a lower dose requirement when used in the treatment of renal disease

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Importantly, sustaining subcutaneous use in CKD patients helps preserve patients’ venous status for future hemodialysis.

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The new data will be presented simultaneously at the Congress of the European Hematology Association (EHA) in Stockholm and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) congress in Istanbul.

These results are in line with those reported from a study in paediatric patients where subcutaneous injections of Aranesp were found to be more painful that those of NeoRecormon in the majority of patients.

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Study design and results

Study design
The study was a comparative, single centre, randomised cross-over trial involving 40 healthy volunteers. After subcutaneous administration of saline (placebo), subjects were randomized to receive identical volumes (0.3ml) and doses (6000 IU or 30µg respectively) of either NeoRecormon  or Aranesp over 2 consecutive study periods according to a cross-over design. For pain evaluations, a qualitative verbal scale ranging from no pain (0) to extremely painful (5) and a 10cm un-graduated Visual Analogue Scale (VAS) (0 = no pain, 10 = maximal pain) were used.

Intent to treat (ITT) Results
Median verbal pain score immediately after injection was 0 for placebo (0.0-1.5), 0 (0.0-1.0) for NeoRecormon   and 2 (1.0-3.0) for Aranesp (p < 0.0001, NeoRecormon vs. Aranesp). The median VAS immediately after injections were 0.4 (0.0-2.3) for placebo, 0.5 (0.0-1.5) for NeoRecormon  and 2.0 (1.4-4.2) for Aranesp (p < 0.0001, NeoRecormon vs. Aranesp). Pain was considered moderate to severe immediately after injection for 12.5 % of subjects on placebo, 5.4% on NeoRecormon  and 37.5 % on Aranesp.

Roche in anaemia
In the field of anaemia therapy, NeoRecormon (epoetin beta) is Roche’s leading treatment for anaemic patients with kidney disease and cancer with over 15 years of experience. Patients who are anaemic and who have renal disease or cancer benefit from treatment with NeoRecormon because it helps give back the energy they need to live the lives they are used to.

Roche is developing the first Continuous Erythropoietin Receptor Activator (CERA) for global commercialisation in renal and cancer related anaemia. CERA is the first of a new class of continuous erythropoietin receptor activators. CERA has a different activity at the receptor which, based on current results, promises to deliver rapid, stable and sustained correction of anemia.

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 2004 sales by the Pharmaceuticals Division totalled 21.7 billion Swiss francs, while the Diagnostics Division posted sales of 7.8 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. Additional information about the Roche Group is available on the Internet (www.roche.com).


References
1. B. Coiffier, F. Berthoux, P. Fiorentini, F. Montestruc. Pain at the injection site; results of a cross-over study comparing epoetin beat and darbepoetin alfa administered subcutaneously in healthy volunteers. Poster 0281. Congress of the European Hematology Association (EHA) Stockholm, 2005
2. G Choukroun, S Gelu-Mantoulet, S Rouanet, A de Chasteigner, F Montestruc, F Berthoux. Pain at the Injection Site: Results of the first cross-over study comparing Epoetin beta and Darbepoetin alfa administered subcutaneously in healthy volunteers. Poster, June 6, European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), Istanbul, 2005.
3. Besarab A, Reyes CM and Hornberger J Am J Kidney Dis 2002 40:3 439-46.
4. Locatelli F, et al: European Best Practice Guidelines Working Group. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 19 (Suppl 2) : 1-47, 2004
5. Schmitt CP, Brummer C, Rosenkranz J et al. Increased injection pain with darbepoetin alpha compared to epoetin beta: a double-blind study in pediatric patients. Poster SU-PO068, 37th Annual Meeting of the American Society of Nephrology; October 29-November 1 2004.