Continuous erythropoietin receptor activator (CERA) is the generic term for drugs in a new class of third-generation erythropoiesis-stimulating agents (ESAs). In the media, these agents are commonly referred to as 'EPO', short for

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bon ...

. CERAs have an extended half-life and a mechanism of action that promotes increased stimulation of

receptors compared with other ESAs. Under the trade name Mircera, Roche Pharmaceuticals received approval from the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) in January 2008 to market a continuous erythropoiesis receptor activator ( methoxy polyethylene glycol-epoetin beta) for the treatment of

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...

in patients with

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, ...

, including in those undergoing

dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...

. This issue appears to have been resolved since Fresenius Medical dialysis clinics in the US are now administering this drug.) Methoxy polyethylene glycol-epoetin beta had been approved by the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...

in August 2007, and was made available in Europe at the start of 2008. In terms of its structure, Mircera is similar to the previous synthetic EPO drugs, except that it is connected to a chemical called

polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...

(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 administered 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 Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

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 sports

Like all previous generations of EPO, the drug has made its appearance as a

doping Doping may refer to: * Doping, adding a dopant to something * Doping (semiconductor), intentionally introducing impurities into an extremely pure semiconductor to change its electrical properties * Aircraft dope, a lacquer that is applied to fabr ...

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. 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 and in October 2008, two-time stage winner Stefan Schumacher, third overall and polka-dot jersey winner

Bernhard Kohl Bernhard Kohl (born 4 January 1982, in Vienna) is an Austrian former professional road bicycle racer and recognized climbing specialist. After the Gerolsteiner team announced they would not be in existence for the 2009 season, Kohl signed with UC ...

, and Leonardo Piepoli tested positive for CERA. Six weeks after the end of the 2008 Olympic Games, the

International Olympic Committee The International Olympic Committee (IOC; french: link=no, Comité international olympique, ''CIO'') is a non-governmental sports organisation based in Lausanne, Switzerland. It is constituted in the form of an association under the Swis ...

(IOC) announced it would be retesting all doping samples from the 2008 Beijing Olympics for CERA. The IOC announced in April 2009 that cyclist Davide Rebellin had tested positive for CERA use. In July 2009, the

Union Cycliste Internationale The ''Union Cycliste Internationale'' (UCI; ; en, International Cycling Union) is the world governing body for sports cycling and oversees international competitive cycling events. The UCI is based in Aigle, Switzerland. The UCI issues rac ...

announced that Danilo Di Luca, who had finished second in the 2009 Giro d'Italia had samples from two stages test positive. In the August 2009 issue of the scientific journal ''Comparative Exercise Physiology'',

Don Catlin Don H. Catlin (born June 4, 1938) is an anti-doping scientist and one of the founders of modern drug-testing in sport. Career Catlin has overseen testing for performance-enhancing drugs at the three most recent Olympics held in the United States ...

, M.D. and colleagues at the Los Angeles-based NGO Anti-Doping Research (ADR) reported that they developed an equine test for CERA. In November 2009, the Olympic 1500 m champion Rashid Ramzi was stripped of his title by the IOC after testing positive for CERA. In July 2010, athlete Erik Tysse gave a positive CERA sample and was later banned for two years by the

IAAF World Athletics, formerly known as the International Amateur Athletic Federation (from 1912 to 2001) and International Association of Athletics Federations (from 2001 to 2019, both abbreviated as the IAAF) is the international governing body fo ...

Illegal use in sports

References

Further reading