Continuous erythropoitin receptor activator

Continuous erythropoitin receptor activator (CERA) is the generic term for drugs in a new class of third-generation erythropoietic-stimulating agents (ESAs). CERAs have an extended half-life and a mechanism of action that promotes increased stimulation of erythropoietin receptors compared with other ESAs. Under the trade name Mircera, Roche Pharmaceuticals received approval from the U.S. FDA in January 2008 to market a continuous erythropoiesis receptor activator (methoxy polyethylene glycol-epoetin beta) for the treatment of anemia in patients with chronic kidney disease, including in those undergoing dialysis [ [http://www.medscape.com/viewarticle/568576] FDA approval ] . (Patent disputes between Amgen, which owns several patents relating to recombinant EPO variants, and Roche are blocking distribution of Mircera in the U.S.) Methoxy polyethylene glycol-epoetin beta previously was approved by the European Commission in August 2007, and was made available in Europe at the start of 2008.

In terms of its structure, Micera is similar to the previous synthetic EPO drugs, except that it is connected to a chemical called polyethylene glycol (PEG), which makes it last longer in the body. According to Roche, the product has the longest half-life of all FDA-approved erythropoiesis-stimulating agents (ESAs): up to 6 times longer than darbepoetin alfa and up to 20 times longer than epoetin. CERAs thus promise both lower dosing -- significant owing to the high inherent cost of manufacturing recombinant protein drugs -- and less frequent injections for patients. ESAs are adminstered via subcutaneous injections, often in doctor's offices for patients who lack the skill or dexterity to inject themselves, so the once- or twice-monthly dosing regimen for CERAs promises fewer costly, inconvenient office visits for patients requiring constant hemoglobin level maintenance for chronic kidney disease.

In clinical trials, CERA dosed every 3 to 4 weeks demonstrated efficacy similar to that of epoetin alfa and darbepoetin alfa in maintaining hemoglobin concentrations within the target hemoglobin range. CERA has generally been well tolerated in clinical trials.

Illegal use in sport

Like all previous generations of EPO, the drug has made its appearance as a doping agent in endurance sport. It was rumoured to be blocked from the kidneys due to its size and therefore undetectable by urine-based doping controls. However, professional cyclist Riccardo Ricco returned a positive A-sample test for Mircera in the 2008 Tour de France and was ejected from the race by his team and arrested by French police [ [http://tour-de-france.velonews.com/article/80269/riccardo-ricc%F2-tests-positive-saunier-duval-team-withdraws] Riccardo Ricco tests positive] . In September 2008, it was reported that samples of around 30 tour riders would be re-tested using a new, more effective test for CERA [ [http://news.bbc.co.uk/sport1/hi/other_sports/cycling/7638711.stm] Lab to re-test Tour blood samples] and in October 2008, two more stage winners tested positive for CERA [ [http://news.bbc.co.uk/sport1/hi/other_sports/cycling/7655977.stm] Tour rocked by new positive tests] . Six weeks after the Games ended, the IOC announced they will be retesting all doping samples from the 2008 Beijing Olympics for CERA. [cite web
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title = IOC to retest all doping samples from Beijing
work =
publisher = Associated Press
date = 2008-10-08
url = http://ap.google.com/article/ALeqM5jIO_zxbrX-Wpy-_J3Tk_yvTOjq9wD93M8P1G0
accessdate = 2008-10-08]

Roche is reported to have worked with sports drug testing authorities at the World Anti-Doping Agency to develop tests for Micera before it became available on the market.

References