Continuous erythropoietin receptor activator (CERA) is the generic term for drugs in a new class of third-generation

erythropoiesis-stimulating agent Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In ...

s (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 bo ...

. 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 F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

received approval from the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) in January 2008 to market a continuous erythropoiesis receptor activator (

methoxy polyethylene glycol-epoetin beta Methoxy polyethylene glycol-epoetin beta is the active ingredient of a drug marketed by Hoffmann-La Roche under the brand name Mircera. Mircera is a long-acting erythropoietin receptor activator (CERA) indicated for the treatment of patients wit ...

) 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, th ...

in patients with chronic kidney disease, including in those undergoing dialysis. 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 o ...

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 we ...

(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 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 Riccardo is a male given name, Italian version of Ricardo or Richard. It also may be a surname. It means "Powerful Leader". It may refer to: People A–L *Riccardo Antoniazzi (1853–1912), Italian violin maker *Riccardo Bacchelli (1891–1985) ...

returned a positive A-sample test for Mircera in the

2008 Tour de France The 2008 Tour de France was the 95th running of the race. The event took place from 5 to 27 July. Starting in the French city of Brest, the tour entered Italy on the 15th stage and returned to France during the 16th, heading for Paris, its regu ...

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 Stefan Schumacher (born 21 July 1981) is a German former professional road racing cyclist. Schumacher won the bronze medal in the road race at the 2007 UCI Road World Championships, two stages in the 2006 Giro d'Italia and two stages in the 2 ...

, third overall and

polka-dot jersey The mountains classification is a secondary competition in the Tour de France, that started in 1933. It is given to the rider that gains the most points for reaching mountain summits first. The leader of the classification is named the King of th ...

winner Bernhard Kohl, and

Leonardo Piepoli Leonardo Piepoli (born 29 September 1971 in La Chaux-de-Fonds, Switzerland) is a former Italian professional road racing cyclist. He most recently rode for on the UCI ProTour, but had his contract suspended in July 2008 during the Tour de Fra ...

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 Swiss ...

(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 Davide Rebellin (9 August 1971 – 30 November 2022) was an Italian professional road bicycle racer, who last rode for UCI Continental team . He was considered one of the finest classics specialists of his generation with more than fifty top t ...

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 racing ...

announced that

Danilo Di Luca Danilo Di Luca (born 2 January 1976) is a former Italy, Italian professional road racing cyclist, best known for winning the 2007 Giro d'Italia, but also for several positive doping tests, the last of which resulting in a lifetime ban from the sp ...

, 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 State ...

, M.D. and colleagues at the Los Angeles-based

NGO A non-governmental organization (NGO) or non-governmental organisation (see spelling differences) is an organization that generally is formed independent from government. They are typically nonprofit entities, and many of them are active in h ...

Anti-Doping Research (ADR) reported that they developed an

equine test Equine drug testing is a form of drug testing applied to performance horses in regulated competition. Most common in racehorses, drug tests are also performed on horses in endurance riding and in international competition such as the Olympics and ...

for CERA. In November 2009, the Olympic 1500 m champion

Rashid Ramzi Rashid Ramzi ( ar, رشيد رمزي) (born July 17, 1980) is a Moroccan-Bahraini track and field athlete competing internationally for Bahrain in the 800 metres and 1500 metres. Ramzi was investigated by the IAAF after the 2008 Summer Olympics ...

was stripped of his title by the IOC after testing positive for CERA. In July 2010, athlete

Erik Tysse Erik Tysse (born 4 December 1980 in Bergen) is a Norwegian race walker. He has competed at four editions of the World Championships in Athletics and represented Norway at the 2008 Summer Olympics and at the 2012 Summer Olympics. He began his int ...

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 for ...

Illegal use in sports

References

Further reading