[ Skip Navigation ]
Typical Hormone


Understanding the function of endogenous hormones and putting them to good use to treat diseases has been one of the great accomplishments of modern medicine. One natural hormone that has turned out to be a blockbuster drug--but not without some controversy--is erythropoietin (EPO).

EPO is a glycoprotein (protein-sugar conjugate) that serves as the primary regulator of red blood cells (erythrocytes) in mammals. It stimulates bone marrow stem cells to differentiate into red blood cells and controls hemoglobin synthesis and red blood cell concentration. Human EPO is a 30,400-dalton molecule containing 165 amino acids and four carbohydrate chains that incorporate sialic acid residues. There are several forms of EPO, designated by Greek letters, that differ only in the carbohydrate content.

In infants, EPO is produced mostly in the liver, but the kidneys become the primary site of EPO synthesis shortly after birth. EPO production is stimulated by reduced oxygen content in arterial blood in the kidneys. Circulating EPO binds to receptors on the surface of erythroid progenitor cells that in turn mature into red blood cells.

Human EPO was first isolated and later purified from urine in the 1970s. Interest in developing clinical uses for EPO led to the discovery of the gene encoding EPO, and several groups devised recombinant DNA methods to produce EPO by the mid-1980s.

Recombinant EPO quickly made it to market to treat anemia resulting from a host of conditions, primarily kidney failure, HIV infection in patients treated with AZT, and cancer chemotherapy. Doses of EPO are given by injection one or more times per week to maintain a normal hematocrit level, the ratio of red blood cell volume to total blood volume. Generally, EPO might be prescribed for any condition where blood oxygen levels are depressed and to help eliminate the potential need for blood transfusions.


OXYGEN BOOSTER David S. Goodsell of Scripps Research Institute created this image of erythropoietin (red) bound to its receptor (blue and green) from coordinates taken from the Protein Data Bank.

Researchers at Amgen and at the Genetics Institute, which became part of Wyeth, were involved in separate efforts to develop recombinant EPO. Amgen received patent protection and began selling the a form of EPO in 1989. The Genetics Institute also tried to commercially develop EPO-, and the result was one of the largest patent fights in U.S. history, according to the Biotechnology Industry Organization. The case was finally settled in favor of Amgen in 1996, giving the company exclusive U.S. rights.

Amgen manufactures and sells its Epogen brand of EPO- in the U.S. for kidney dialysis patients. Johnson & Johnson has a long-standing licensing agreement with Amgen to sell its Procrit brand, manufactured by Amgen, for nondialysis uses in the U.S. through J&J's affiliate Ortho Biotech. J&J also sells its Eprex brand, manufactured by Ortho Biologics, outside the U.S. for all uses through Janssen-Cilag. The Amgen-J&J relationship has been a rocky one, as the two companies have battled over breaches in the EPO licensing agreement.

Amgen's Epogen had 2004 U.S. sales of $2.6 billion, while J&J's Procrit and Eprex had combined 2004 sales of $3.6 billion. Other versions of EPO include Roche's NeoRecormon brand of recombinant EPO-, which had 2004 European sales of $1.7 billion. Transkaryotic Therapies, Cambridge, Mass., has developed EPO-, and the company recently won a patent fight with Amgen over the right to sell it in Europe. Transkaryotic Therapies will start offering it as the Dynepo brand in 2006. Some generic versions of EPO are also being marketed outside the U.S.

Amgen also has developed a second-generation anemia drug, darbepoetin, which is similar to EPO but contains two additional sialic acid-containing carbohydrate chains. The additional carbohydrate groups increase the activity of the hormone and slow its rate of clearance from the body; thus a dose is required about half as often as EPO. Amgen sells darbepoetin-a as the Aranesp brand to treat anemia related to cancer chemotherapy and kidney failure. Worldwide, Aranesp sales were $2.5 billion in 2004.

Despite improving the quality of life for hundreds of thousands of sick people, EPO has a dark side. Endurance athletes such as cyclists, distance runners, and cross-country skiers have misused recombinant EPO as a performance-enhancing drug. Clinical studies have shown that EPO can provide a 5 to 15% boost in athletic performance by producing extra red blood cells to improve oxygen uptake and thus aerobic power.

But EPO used this way can be lethal. The additional red blood cells can cause "hyperviscosity," or thickened blood, particularly when athletes are dehydrated, raising the risk for heart attacks and strokes. The deaths of a few dozen elite athletes, especially cyclists, have been linked to EPO use since the 1980s.

A natural way to increase EPO production is altitude training, made famous by distance runners. Exercise physiologists have known for some time that the body responds to the thinner air above 6,000 feet by increasing EPO concentration and red blood cell volume after a few weeks. Some studies indicate that just over 40% of runners respond to altitude training.

Enzyme immunoassays can provide a measure of serum EPO levels, but the tests can't determine if the EPO is natural or produced recombinantly and injected by unscrupulous athletes. The World Anti-Doping Agency has now developed combination urine and blood tests that can detect EPO abuse by athletes.—STEVE RITTER


The Top Pharmaceuticals
That Changed The World
Vol. 83, Issue 25 (6/20/05)
Table Of Contents

Epoetin Alfa


  • Erythropoietin (EPO)


  • Erythropoietin (EPO)

CAS Registry

  • 113427-24-0

Other names

  • Procrit
  • Epogen
  • Eprex


1989, Amgen


  • Combined 2004 sales of all EPO products was approximately $11 billion