Roche announces successful completion of four pivotal Phase III clinical trials for CERA

Key milestone reached towards filing for renal anemia indication in 2006

Basel, 16 December 2005, Roche, a world leader in biotechnology, today announced that all four maintenance studies of the pivotal Phase III renal program for its unique long-acting anti-anemia agent, CERA, have been successfully completed. CERA is the first and only Continuous Erythropoietin Receptor Activator and the only anti-anemia drug to have ever studied long dosing intervals of once every four weeks in all patients for its initial filing.

The final two studies examining correction of anemia in patients with chronic kidney disease on dialysis and not on dialysis are nearing completion.

In these maintenance studies, patients on dialysis and on stable maintenance treatment of anemia with epoetin or darbepoetin were randomized to continue their treatment or switch to CERA given once every two weeks or once every four weeks. The maintenance studies met their primary endpoints and show that both intravenous and subcutaneous CERA, when given at extended dosing intervals, was effective in maintaining Hb levels. Generally, the safety profile is characteristic of the population under study. The full review of the benefit-risk assessment of CERA will be made by the Health Authorities after filing in 2006.

“This is a key milestone towards submitting a dossier for the registration of CERA to regulatory authorities in the United States and European Union next year,” said Eduard Holdener, Global Head Pharmaceutical Development, Roche. “The administration of CERA up to once every four weeks means that we can potentially offer patients a convenient and efficacious medication throughout the many stages of their renal disease.”

The aims of the Phase III program were to confirm the efficacy of CERA at extended administration intervals for the correction of anemia and the maintenance of Hb levels and to demonstrate its long-term safety and tolerability. The Phase II - III program is the largest program ever undertaken for a drug treating renal anemia, and involving more than 2,700 patients from 29 countries.

CERA
CERA is a new drug under development for the treatment of anemia in chronic kidney disease patients. It is the first and only Continuous Erythropoietin Receptor Activator. This means that the activity of CERA at the receptor sites involved in stimulating red blood cell production is different from what has been observed for erythropoietin, and this distinct molecular interaction is believed to have an essential role in providing targeted, stable and sustained control of anemia.

About Anemia
Anemia is a complication associated with patients suffering from Chronic Kidney Disease from those with early stage illness to those with end stage kidney failure requiring dialysis. Anemia refers to patients experiencing a lower than normal level of red blood cells or the hemoglobin in them. Hemoglobin enables red blood cells to carry oxygen throughout the body and therefore, when the body is starved of the oxygen it requires, extreme fatigue sets in along with dizziness, pale skin and other symptoms. Other serious clinical complications will appear as the body works harder to compensate for the lack of oxygen.

Normally, when the body senses a decrease in the oxygen available to the body, more erythropoietin (a protein produced by the kidneys) is created. This protein stimulates the production of oxygen-carrying red blood cells in the bone marrow which raises the red blood cell count. When this natural mechanism is hindered (as in patients with kidney disease), it is necessary to stimulate the receptors in the bone marrow to produce red blood cells with agents such as CERA, which will be the first – and only – continuous erythropoietin receptor activator.

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).

Further Information:
- Clinical trials (http://www.roche-trials.com/)


Notes to the Editor:
The Phase III study program consisted of two correction and four maintenance studies. Correction is a term that is used to describe the initial phase of treatment for renal patients who have been diagnosed with anemia but who have not previously received treatment with an agent to increase their Hb level. Maintenance refers to keeping Hb levels in a defined range over time in patients whose Hb levels have been corrected.

In maintenance, the primary endpoint was the change in haemoglobin (Hb) concentration between baseline and the evaluation period:

The first study was designed to evaluate IV CERA in the maintenance of Hb levels in CKD patients on dialysis previously maintained on IV epoetin. IV epoetin was dosed up to three times weekly compared to CERA dosed once every two weeks or once every four weeks.
The second study was designed to evaluate SC CERA in the maintenance of Hb levels in CKD patients on dialysis previously maintained on SC epoetin. SC epoetin was administered up to three times weekly, compared to CERA dosed either once every two weeks or once every four weeks.
The third study was designed to evaluate IV CERA in the maintenance of Hb levels in CKD patients on dialysis previously maintained on IV darbepoetin alfa. Darbepoetin alfa was dosed once a week or once every two weeks compared to CERA dosed once every two weeks.
The fourth study was designed to evaluate SC or IV CERA in a pre-filled syringe in the maintenance of Hb levels in patients on dialysis previously maintained on epoetin. Epoetin was administered up to three times weekly compared to CERA administered once every two weeks.

Contact Information

Katja Prowald

Head R&D Communications

Roche

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