Japan's Astellas Pharma and Britain's GlaxoSmithKline are competing to develop a new kind of medicine that boosts production of red blood cells by making the body think it is at high altitude.
Their experimental drugs - both given as pills - could create a major new market in treating anemia and other serious conditions, including circulatory problems and wound damage.
They may also attract unscrupulous athletes seeking a handy oral alternative to injections of EPO
, or erythropoietin, the blood enhancer that has become a byword for doping in cases involving cyclist Lance Armstrong and others.
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So far, the rival pills are not generally on investors' radar, but they could become significant challengers in an anemia therapy market that is currently dominated by EPO products with combined sales of close to $8 billion a year.
GSK Chief Executive Andrew Witty recently highlighted his company's pill, dubbed GSK 1278863, as one of the two most exciting and innovative products in the development pipeline alongside a promising cancer vaccine called MAGE-A3.
"It is a tablet which makes the body think it is at 5,000 feet. When you go and exercise at altitude you produce a lot of red blood cells, so it has all sorts of potential applications in terms of helping people with blood disorders," he told a National Health Service meeting last month.
GSK is testing its drug in Phase II clinical trials. That puts it behind Astellas and its partner FibroGen, which launched final-stage Phase III tests in December of their drug, known as FG-4592 or ASP1517, as an anemia treatment in patients with chronic kidney disease.
Mike Allen, head of urology and nephrology at Astellas, said the new drug marked a major advance compared to EPO, since it did not raise blood pressure - a concern with EPO. And since it can be given orally at home, it should be particularly suitable for kidney patients who are not on hospital dialysis.
"We are very excited about this product and its potential. It is a priority in our portfolio and we do think that as a novel mechanism for this medical need it is very creative and shows great promise," Allen said in an interview.
Astellas placed a big bet on the new approach in 2006 when it licensed the European and Japanese rights to FG-4592 from private U.S. firm FibroGen in a deal potentially worth more than $2 billion. FibroGen retains rights to the drug in the United States and other markets, and for uses other than anemia.
Another private U.S. company, Akebia Therapeutics, also has a similar HIF-prolyl hydroxylase inhibitor in Phase II tests.
Peter Ratcliffe of the University of Oxford, whose team discovered the prolyl hydroxylase enzymes targeted by the new drugs in 2001, sees a role for them in multiple areas.
In addition to treating anemia, they might help with major circulatory problems such as angina or bad circulation in the legs, aid repair to the body after tissue is damaged, and reduce inflammatory problems such as colitis in the gut.
The new drugs mimic the body's response to hypoxia, or low oxygen levels, by increasing the natural production of EPO in the kidneys.
"The potential advantage over EPO is that these drugs are pills and they also do other things that support the action of EPO, including facilitating the absorption of iron," Ratcliffe said. "It could be an important new area of medicine, which is exciting to explore."
Ratcliffe, who is Nuffield Professor of Clinical Medicine at Oxford, also works as a consultant to GSK.
Current injectable EPO stimulating agents have been under a cloud for some years due to cardiovascular safety concerns. As a result, the global market has shrunk from a peak of $12 billion in 2006, although products like Amgen's Epogen and Aranesp remain multibillion-dollar sellers.
Doctors will be keeping a close watch on potential safety issues with the new pills, too, as they advance through large-scale clinical testing. So far, there are no signs of cardiovascular problems. But there is a potential for unwanted side effects given the generalized way in which the drugs work.
The challenge will be to balance the local and general effects of medicines that, depending on dose, mimic the effects of being at between 5,000 and 15,000 feet, Ratcliffe said.
Side effects may be less of a concern for sport cheats.
Allen said Astellas would do whatever was necessary to ensure its new drug was not abused, although it is has not yet held talks with the World Anti-Doping Agency (WADA).
GSK, meanwhile, told WADA last year that it had an unnamed experimental drug that could boost red blood cell production - the first such notification under a new agreement designed to clamp down on illicit drug use in sport.
A company spokesman said it was GSK's policy not to identify individual compounds under the deal with WADA.
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