Roche Submits Application to FDA to Market CERA for the Treatment of Renal Anaemia

BASEL, Switzerland, April 20 /PRNewswire/ --

-- Submission Based On Full Phase III Program Including Four Maintenance and Two Correction Trials with Dialysis and Non-Dialysis Chronic Kidney Disease Patients

Roche a world leader in biotechnology today announced it has submitted a Biological License Application (BLA) to the U.S. Food and Drug Administration (FDA) to market CERA for the treatment of anaemia associated with chronic kidney disease (CKD) including patients on dialysis and not on dialysis.

CERA, an innovative investigational anti-anaemia agent, 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 that observed with traditional epoetins. This distinct molecular interaction is believed to have a role in providing targeted, stable and sustained control of anaemia. CERA is the only anti-anaemia treatment to have been studied with long dosing intervals, up to once every four weeks, for its initial filing.

"The US filing for CERA is the next step along the path to making this important therapy available," said Eduard Holdener, Global Head Pharmaceutical Development, Roche. "One of the primary endpoints we investigated was haemoglobin response and levels over time as we know that physicians find it challenging to keep patients' haemoglobin in a recommended target range despite their best efforts.1,2 We believe CERA's clinical profile is able to address this issue."

The BLA submission is based on the largest clinical programme ever undertaken for a drug treating renal anaemia. It included six Phase III trials conducted in 29 countries and involved 2,400 patients. The studies investigated the efficacy of both intravenous and subcutaneous CERA administered up to once every four weeks.

Last December the four maintenance studies from Phase III were successfully completed and very recently Roche completed the last two studies to treat (correct) anaemia. The studies met their primary endpoints and showed that both intravenous and subcutaneous CERA, when given at extended dosing intervals, were effective in correcting anaemia according to best practice guidelines, and in maintaining Hb levels following correction. Overall, the safety profile was characteristic of the population under study.

About Anaemia

There are approximately 530,000 US CKD patients not on dialysis and 324,000 US patients on dialysis who suffer from anaemia. Anaemia refers to patients experiencing a lower than normal level of red blood cells or the haemoglobin in them. Haemoglobin 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 -- in particular, the heart -- 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 to produce red blood cells which is what CERA is designed to do. The goal of treatment is to increase haemoglobin back to a desirable level and maintain that level over time.

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 (http://www.roche.com).

All trademarks used or mentioned in this release are protected by law.

    
    Roche Group Media Office
    Phone: +41-61-688-8888 / e-mail: basel.mediaoffice@roche.com
    - Baschi Durr
    - Alexander Klauser
    - Daniel Piller (Head of Roche Group Media Office)
    - Katja Prowald (Head of R&D Communications)
    - Martina Rupp

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 anaemia 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.

The first correction study in 182 dialysis patients examined the Hb response rate to intravenous administration of CERA in patients who were treated once every two weeks during the first 24 weeks. Thereafter, the patients were maintained on the same schedule or provided with a once every-four-week dosing regimen for the remaining 28 weeks. These CERA patients were compared to patients who were treated with epoetin at the approved three-times-weekly schedule.

The second correction study in 324 chronic kidney disease patients not on dialysis, evaluated the Hb response rate achieved during the first 28 weeks, and the change in Hb concentration between the baseline and the 10-week evaluation period. Patients' anaemia was corrected with subcutaneous (SC) CERA given once every two weeks. Then during the 24-week maintenance phase two dosing intervals of CERA were provided: once every two weeks or once every four weeks. These patients were compared to patients treated with darbepoetin alfa given once a week or once every two weeks according to its label.

    
    (1) Lascon E et al: Effect of Variability in Anemia Management on
        Hemoglobin Outcomes in ESRD. Am J Kidney Dis:41:111-124, 2003.
    (2) Fishbane S and Berns J: Hemoglobin cycling in hemodialysis patients
        treated with recombinant human erythropoietin. Kidney International,
        Vol. 68 (2005), pp. 1337-1343.

Web site: http://www.roche.com

Baschi Durr, Alexander Klauser, Daniel Piller - Head of Roche Group Media Office, Katja Prowald - Head of R&D Communications, or Martina Rupp, Roche Group Media Office, +41-61-688-8888, basel.mediaoffice@roche.com