Mircera (C.E.R.A.) first drug to directly convert dialysis patients to once-monthly dosing schedule

First public presentation of Phase III data from largest ever renal anaemia clinical development program

Basel, 17 July 2006 - For the first time, clinical studies show that dialysis patients treated with short-acting and frequently administered epoetin anti-anaemia drugs can be directly switched to a once-monthly treatment resulting in stable haemoglobin (Hb) levels.1,2 This new drug in development is Mircera Roche’s continuous erythropoietin receptor activator (C.E.R.A.) and the once-monthly dosing approach – never before studied in this way – is a milestone in anaemia management.
Dialysis patients can receive existing anti-anaemia treatments as frequently as several times a week, depending on the drug and patient status.3 Roche’s once-monthly C.E.R.A. could have a positive impact on the management of anaemia in dialysis patients by reducing work loads and offering greater efficiencies.1,2

The results of three Phase III ‘maintenance’ studies – part of the largest clinical development program ever undertaken for a drug treating renal anaemia – were presented at the annual meeting of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) in Glasgow, Scotland. These included two studies using epoetin alfa/beta as a comparator and one study using darbepoetin alfa.1,2,4

“This was the first Phase III registration study that examined a once-monthly dosing interval. We were gratified to see that C.E.R.A. maintained stable haemoglobin levels during the evaluation and extended phases in these dialysis patients,” said Dr. Nathan Levin, Medical and Research Director of the Renal Research Institute, New York and one of the lead investigators who presented the results of the first study. “Haemoglobin plays an important role in improving physical function and reducing the likelihood of heart disease, but maintaining stable haemoglobin levels can be a clinical challenge. These results with this C.E.R.A. indicate the therapy may be a major step forward in the practical treatment of anaemia”.

Roche filed applications with the regulatory authorities in the United States and the European Union in April for the treatment of anaemia associated with chronic kidney disease including patients on dialysis and not, based in part on this data. Results from the remaining Phase III correction studies will be announced later this year.

About the Phase III Maintenance Studies
The primary objective of the studies was to demonstrate that intravenous (IV) or subcutaneous (SC) C.E.R.A. can maintain Hb concentrations in dialysis patients on prior epoetin alfa/beta or darbepoetin alfa therapy.1,2,4 The aim of these studies is to demonstrate efficacy by proving that this C.E.R.A. is at least as effective as an existing therapy based on their approved administration schedules.1,2,4 This is important as these studies involved directly converting or switching patients from very frequent therapy to a once-monthly regimen.1,2,4

In these maintenance studies, which aim to keep Hb levels in a defined range over time in dialysis patients whose Hb levels have been corrected, patients were randomized to continue their frequent treatment or convert directly to C.E.R.A. given once every two weeks or once-monthly.1,2,4 The primary endpoint was the mean change in Hb between baseline and the evaluation period. In these trials, dosage was adjusted to maintain Hb +/-1.0 g/dL of the baseline level.1,2,4

* The first study was designed to evaluate IV C.E.R.A dosed once every two weeks or once-monthly in the maintenance of Hb levels in dialysis patients previously maintained on IV epoetin alfa/beta dosed up to three times weekly.1 Close to 90 percent of patients were receiving a three-time weekly dose of epoetins at the time they were converted.1 The difference between once-monthly IV C.E.R.A. and epoetin at short dosing intervals in the mean change in Hb was negligible (0.05g/dL), which shows a steady maintenance of Hb. According to the study protocol, these results demonstrate that IV C.E.R.A. once monthly is as effective as IV epoetin in maintaining Hb levels. (p<0.0001).1
* The second study mirrored the first and evaluated SC C.E.R.A at the same dosing intervals and patient population previously maintained on SC epoetin alfa/beta.2 The difference between once-monthly SC C.E.R.A. and epoetin in the mean change in Hb was negligible (-0.02g/dL) demonstrating a steady maintenance of Hb. According to the study protocol, these results demonstrate that SC C.E.R.A. once monthly is as effective as SC epoetin in maintaining Hb levels. (p<0.0001).2
* The third study evaluated IV C.E.R.A dosed once every two weeks in the maintenance of Hb levels in dialysis patients previously maintained on IV darbepoetin alfa.3 Darbepoetin alfa was dosed once a week or once every two weeks.3 The difference between IV C.E.R.A. and darbepoetin in the mean change in Hb was negligible (0.18g/dL) demonstrating a steady maintenance of Hb. According to the study protocol, these results demonstrate that IV C.E.R.A. twice monthly is as effective as IV darbepoetin alfa in maintaining Hb levels. (p<0.0001).3
* The data from these three multi-centre, Phase III maintenance studies showed that both IV and SC administration of this C.E.R.A. twice a month or once monthly maintained haemoglobin levels in a seamless fashion in dialysis patients.1,2,4 C.E.R.A. was well-tolerated, with a safety profile characteristic of the patient population.1,2,4

About C.E.R.A.
Roche’s innovative investigational anti-anaemia agent is the first continuous erythropoietin receptor activator (C.E.R.A.), which is a new class of drugs. Its activity at the receptor sites involved in stimulating red blood cell production is different from that observed with traditional epoetin drugs. The distinct molecular interaction of this C.E.R.A. is believed to play an important role in providing targeted, stable and sustained control of anaemia.

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).

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References:
1. N. Levin, S. Fishbane, S. Zieg, G. Nassar, J. Moran, G. Villa, F. Dougherty. Poster Submitted to EDTA. Intravenous (IV) C.E.R.A. (Continuous Erythropoietin Receptor Activaor) Administered Once Every 2 Weeks Or Once Monthly Maintains Haemoglobin (Hb) Levels in Patients With Chronic Kidney Disease, 2006, Glasgow, Scotland.
2. W. Sulowicz, F. Locatelli, J. Balla, B. Csiky, C. Rikker, J. Aldigier, F. Dougherty. Poster Submitted to EDTA. Subcutaneous (SC) C.E.R.A. (Continuous ErythropoietinReceptor Activator) Administered Once Every 2 Weeks or Once Monthly Maintains Haemoglobin (Hb) Levels in Patients with Chronic Kidney Disease (CKD) on Dialysis, 2006, Glasgow, Scotland.
3. National Kidney Foundation: K/DOQI Clinical Practice Guidelines: 2000 Update.
4. B. Canaud, J. Braun, F. Locatelli, G. Villa, B. Vlem, D. Guajardo, F. Dougherty. Intravenous (IV) C.E.R.A. (Continuous Erythropoietin Receptor Activator) administered once every 2 weeks maintains stable haemoglobin (Hb) levels in patients with chronic kidney disease (CKD) on dialysis, 2006, Glasgow, Scotland.

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Katja Prowald

Head R&D Communications

Roche Group

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