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

GlaxoSmithKline reported to have already alerted WADA to product that will be used to treat conditions such as anameia

by Simon_MacMichael   April 20, 2013  

London 2012 Anti-Doping Laboratory (picture credit LOCOG)

Tags

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.

6 user comments

Oldest firstNewest firstBest rated

It would be nice if the manufacturers could put some chemical marker in the product which would show up in tests, its a shame the UCI cant fund some system for doing that.

posted by Welsh boy [102 posts]
21st April 2013 - 19:33

like this
Like (8)

To be fair though Welsh boy the proportion of the EPO in the world and indeed the proportion of this drug that will be used by cheating sportsmen must be a tiny fraction of the whole. Given that it seems a tad unreasonable to ask drug companies to increase the development costs of drugs to add such a marker especially given that the cost would be passed on to taxpayers and the sick around the world who need such drugs for their theraputic benefits.

Tony Farrelly's picture

posted by Tony Farrelly [4132 posts]
21st April 2013 - 21:56

like this
Like (7)

The development cost of drugs now is astronomical. Since this compound would be available in pill form, it would be relatively inexpensive to add a marker to the standard filler mix used to provide the vast bulk of a tablet. So I agree with Welsh Boy that it would be socially responsible to do so. By including an 'inert' marker in the formulation before trials, the additional development cost would be minimised, and limited to the initial design of such a marker. If the marker were a standard addition, as it is in things like explosive manufacture the cost and inconvenience would soon be absorbed.

Unfortunately in order to receive certification and legal protection of a drug formulation, it has to be published, and can therefore be duplicated by other labs, who may choose to ignore licensing terms and things like markers when producing drugs intended for abuse. For instance the drug GSK terminated in trial for potentially toxic side effects that is now showing up in tests. GSK will have verifiably destroyed all samples as part of the process, so it's not coming from a legal lab, but GSK will have published the trial and formulation, as required. I'm not saying the data and formulations shouldn't be published, only that fully open access allows access to the bad guys as well the protection it affords the rest of us.

posted by robdaykin [159 posts]
22nd April 2013 - 7:48

like this
Like (7)

The issue isnt so much the kosher stuff - its the versions that flood onto the market, widely available over the internet, created using the forumulae that gets leaked and published.

posted by Sam1 [212 posts]
22nd April 2013 - 10:55

like this
Like (7)

From memory, there was some cooperation with drugs companies when CERA, the next generation EPO, came out. I remember that at least one rider got caught because the drugs company had inserted a molecular marker in it which could be picked up in testing. No idea whether this will continue though as it's presumably expensive but nevertheless a good idea.

posted by Sadly Biggins [263 posts]
22nd April 2013 - 12:05

like this
Like (8)

tony_farrelly wrote:
To be fair though Welsh boy the proportion of the EPO in the world and indeed the proportion of this drug that will be used by cheating sportsmen must be a tiny fraction of the whole. Given that it seems a tad unreasonable to ask drug companies to increase the development costs of drugs to add such a marker especially given that the cost would be passed on to taxpayers and the sick around the world who need such drugs for their theraputic benefits.

As I understood it, that was exactly what GSK are doing under the Wada co-operation agreement, in so much as they are sharing the formulation/markers so that ADAs can develop testing based on the biochemical signature left by the product. Thus that reduces the time to develop tests and allows GSK to solve the riddle of where and how their products are being leaked and bootlegged to protect their own IP.

http://www.chasingwheels.com - Chasing Wheels, the journal of Britain's least competitive cyclist

posted by leguape [38 posts]
22nd April 2013 - 14:23

like this
Like (10)