EPO competitor pill from UK's biggest drugs firm fools body into behaving as if at altitude

A new drug being developed by Britain’s largest pharmaceutical company aims to trick the body into boosting its production of red blood cells by making it behave as though it is at altitude, reports Reuters, with the World Anti-Doping Agency (WADA) believed to have already been alerted to its potential performance enhacing benefits.

Reuters says that West London-based GlaxoSmithKline (GSK) last year became the first pharmaceutical business in the world to notify the agency of a new drug under an agreement aimed at fighting doping in sport.

While a company spokesman said the agreement meant GSK was unable to identify specific compounds, the one notified to WADA is said to be a drug that enhances the production of red blood cells.

GSK’s drug, once it comes to market, will compete with products such as EPO in an $8 billion global market for treatment of conditions such as anaemia, but which clearly also has potential performance-enhancing benefits for athletes.

Currently, the market is dominated by US-based Amgen – coincidentally, sponsor of the Tour of California – although it has eased back from a peak in sales of $12 billion in 2006, te reduction partly explained by concerns over side-effects.

GSK, which operated the anti-doping laboratory in Brentwood, Essex, for last summer’s Olympic and Paralympic Games in London, is competing with Japan’s Astellas Pharma to be first to market with the drug, in both cases being developed to be taken in oral form as a tablet.

The British firm’s product, currently going by the name GSK 1278863 and undergoing Stage II clinical trials, was last month highlighted at a National Health Service meeting by its chief executive, Andrew Witty, as one of the two products it currently has under development for which it has the highest hopes, the other being a cancer vaccine.

"It is a tablet which makes the body think it is at 5,000 feet,” he explained. “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."

Japanese company Astellas is developing its own drug, aimed primarily at treating patients with chronic kidney disease, in partnership with California-based FibroGen. It entered Stage III clinical trials last December, putting it ahead of GSK’s drug in terms of their developmental timetable.

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,” commented Mike Allen, head of urology and nephrology for Astellas. “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."

Peter Ratcliffe, Nuffield Professor of Clinical Medicine at the University of Oxford, who led researchers who discovered the prolyl hydroxylase enzymes that the drugs currently in development are intended to act upon, outlined their possible benefits.

"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," explained Professor Ratcliffe, who is also engaged as a consultant by GSK. "It could be an important new area of medicine, which is exciting to explore."

GSK’s new drug is not believed to carry the same potentially harmful side-effects on the cardiovascular system as EPO, which is widely believed to have been at least partly responsible for the early deaths of a number of cyclists around a decade ago, some highlighted in this 2004 article from the Guardian.

However, there are some issues that still need to be fully understood, with Professor Ratcliffe saying that among those is one relating to dosage, given that the drug could replicate the effect of the body being at 5,000 feet or 10,000 feet, for example, depending how much of it was administered.