Hoffmann-La Roche Inc. Release: C.E.R.A. Administered Up To Once Every Four Weeks Maintained Stable Hemoglobin Levels In Dialysis Patients With Chronic Kidney Disease

SAN DIEGO, and NUTLEY, N.J., Nov. 18 /PRNewswire/ -- Roche's investigational treatment C.E.R.A., administered once every two weeks or once every four weeks, was shown to maintain stable hemoglobin (Hb) levels in dialysis patients who had been taking short-acting, frequently administered epoetin, according to new data from two phase III trials presented today at the 39th Annual Meeting of the American Society of Nephrology in San Diego, CA.

The C.E.R.A. trials represent a milestone in anemia management, as this is the first time an anti-anemia therapy has been studied in dosing intervals of up to once every four weeks for its initial Food and Drug Administration (FDA) filing.

"Maintaining hemoglobin levels within target range is important for the physical well being of the patient," said Nathan Levin, M.D., Medical and Research Director of the Renal Research Institute, New York and one of the lead investigators. "Furthermore, these new data showing that factors such as age, gender and diabetic status of the patient do not diminish the impact of C.E.R.A., are important, but not unexpected information."

About PROTOS and MAXIMA Phase III Maintenance Studies

The primary objective of the multi-center, phase III maintenance studies, PROTOS (Patients Receiving C.E.R.A. Once a Month for the MainTenance Of Stable Hemoglobin) and MAXIMA (Maintenance of HAemoglobin EXcels with IV Administration of C.E.R.A.), was to demonstrate that subcutaneous (SC) and intravenous (IV) C.E.R.A. can maintain Hb concentration in dialysis patients previously maintained on epoetin alfa/beta therapy when converted from more frequent dosing to either once every two weeks or once every four weeks with C.E.R.A. Maintenance refers to the ability of C.E.R.A. to keep dialysis patients' Hb levels within target range over a defined period of time.

In the studies, patients were randomized to continue their current treatment regimen or convert to C.E.R.A. once every two weeks or once every four weeks. The primary endpoint was the mean change in Hb between baseline and the evaluation period. (Evaluation occurred at week 28 or 29 following initiation of C.E.R.A. depending on the study protocol.)

In addition, subgroup analyses were conducted for the PROTOS and MAXIMA trials to determine the impact of age, gender and diabetic status on mean Hb levels during the evaluation period in patients receiving C.E.R.A. once every four weeks. In these trials, dosage was adjusted to maintain Hb plus or minus 1.0 g/dL of the baseline level.

Details for the studies are as follows: * SC C.E.R.A. (Continuous Erythropoietin Receptor Activator) Once Every 2 Weeks or Once Monthly Maintains Stable Hb Levels after Converting Directly from SC Epoetin 1-3 Times per Week in Patients with CKD on Dialysis (PROTOS) [SA-PO207] The PROTOS study compared the efficacy of SC C.E.R.A. in maintaining stable Hb levels in dialysis patients converted directly from SC epoetin alfa or beta administered up to three times weekly to C.E.R.A. administered once every two weeks or once every four weeks. For patients receiving C.E.R.A once every two weeks, the mean difference in Hb from baseline was 0.52 g/dL in the evaluation period (weeks 29-36) and 0.68 g/dL during the follow-up period (weeks 37-52). For patients receiving C.E.R.A. once every four weeks the mean difference in Hb levels were 0.57g/dL for the evaluation period and 0.76 g/dL during follow-up. Mean difference in Hb from baseline for epoetin treated patients was 0.57 g/dL for the evaluation period and 0.68 g/dL during follow-up. These data demonstrate that once every four week dosing of C.E.R.A. was as effective as frequently dosed (1-3 times per week) epoetin alfa or beta. * SC C.E.R.A. (Continuous Erythropoietin Receptor Activator) Administered up to Once Monthly in Patients with CKD on Dialysis Maintain Adequate Hb Levels Regardless of Age, Gender or Diabetic Status (PROTOS) [SA-PO210] In this subgroup analysis of the PROTOS trial, the mean Hb levels between patients taking C.E.R.A. once every four weeks and frequently dosed epoetin were similar regardless of age (patients <65 11.42 g/dL (1.07), 65-74 11.42 g/dL (1.05), greater than or equal to 75 11.30 g/dL (1.05). Data from a subgroup analysis by gender showed that Hb levels were consistent for women and men (11.37 g/dL (1.16) vs 11.41 g/dL (0.99) respectively). Similar results were seen in an analysis by diabetic status (11.55 g/dL (1.15) for patients with diabetes vs 11.33 g/dL (1.02) for patients without diabetes). * IV C.E.R.A. (Continuous Erythropoietin Receptor Activator) Once Every 2 Weeks or Once Monthly Maintains Stable Hb Levels after Converting Directly from IV Epoetin 1-3 Times per Week in Patients with CKD on Dialysis (MAXIMA) [SA-PO205] The MAXIMA study investigated the efficacy of IV C.E.R.A. in maintaining stable Hb levels in dialysis patients converted directly from frequently dosed IV epoetin alfa or beta to C.E.R.A. administered once every two weeks or once every four weeks. The mean difference in Hb from baseline in patients treated with C.E.R.A. once every two weeks was 0.60 g/dL in the evaluation period (weeks 29-36) and 0.79 g/dL during the follow-up period (weeks 37-52). For patients receiving C.E.R.A. once every four weeks the mean differences in Hb levels were 0.56 and 0.71 g/dL respectively for the evaluation period and follow-up. Data for epoetin treated patients showed a mean difference of 0.55 and 0.66 g/dL respectively. These data demonstrate that once every four week dosing of C.E.R.A. was as effective as frequently dosed (1-3 times per week) epoetin alfa or beta. * Adequate Hb Levels are Maintained with IV C.E.R.A. (Continuous Erythropoietin Receptor Activator) Administered up to Once Monthly in Patients with CKD on Dialysis Irrespective of Age, Gender or Diabetic Status (MAXIMA) [SA-PO206] This subgroup analysis of the MAXIMA study showed that the mean Hb levels between patients taking C.E.R.A. once every four weeks and frequently dosed epoetin were similar regardless of age (patients <65 11.95 g/dL (1.11), 65-74 11.41 g/dL (1.18), greater than or equal to 75 11.56 g/dL (0.89). Data from a subgroup analysis by gender showed that Hb levels were consistent for women and men (11.76 g/dL (1.05) vs 11.75 g/dL (1.16) respectively). Similar results were seen in an analysis by diabetic status (11.73 g/dL (1.05) for patients with diabetes vs 11.77 g/dL (1.15) for patients without diabetes). About Renal Anemia

Renal anemia is a common and debilitating complication of chronic kidney disease (CKD) that's characterized by a low concentration of hemoglobin (Hb) in the blood. Inadequate Hb levels deprive the body's tissues of oxygen and can lead to serious complications and death if left untreated. Treatment guidelines suggest doctors elevate and maintain these Hb levels within a specific range, as both inadequate and excessive Hb levels can be associated with complications. Most CKD patients receive anti-anemia treatment with currently available short-acting therapies as often as 26-156 times a year to keep Hb levels within target range.

About the Phase III Clinical Trial Program

The C.E.R.A. phase III clinical program was part of the largest clinical development program ever conducted for the initial Food and Drug Administration (FDA) filing of a treatment for renal anemia. The program consisted of two initiation/correction and four conversion/maintenance studies of both SC and IV C.E.R.A. at extended administration intervals.

Safety Information

In the PROTOS and MAXIMA trials, the most frequently reported adverse events were hypertension and procedural hypotension and diarrhea and nasopharyngitis, respectively. Erythropoietic therapies may increase the risk of cardiovascular and other thrombotic events. Pure Red Cell Aplasia (PRCA) has been observed in patients treated with erythropoietin therapy. To date, PRCA has not been observed with C.E.R.A. in clinical trials.

About C.E.R.A.

Roche's innovative investigational anti-anemia agent is the first continuous erythropoietin receptor activator. Its activity at the receptor sites involved in stimulating red blood cell production is different from that observed with traditional epoetin drugs.

Roche filed applications with the regulatory authorities in the United States and the European Union in April of this year seeking approval for use of the treatment in anemia associated with CKD in patients on dialysis and not on dialysis.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for OlderWorkers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.

Hoffmann-La Roche Inc.

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