* Drugs mimic body's response to being at high altitude
* Experimental tablets an alternative to injections of EPO
* Astellas and partner FibroGen in lead with Phase III pill
* GSK CEO says excited by potential of its Phase II product
By Ben Hirschler
LONDON, April 19 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 anaemia 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.
So far, the rival pills are not generally on investors'
radar, but they could become significant challengers in an
anaemia 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 anaemia 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 anaemia.
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 anaemia, 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 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 generalised 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.