The failure of rival heart drugs has put the spotlight on a novel GlaxoSmithKline compound that will reach a critical stage of testing this year, after languishing in development for years.
Darapladib, which Glaxo discovered with Human Genome Sciences Inc., targets an enzyme called Lp-PLA2 that is linked to artery-clogging plaques.
Industry analysts at Credit Suisse reckon the drug could achieve annual sales of $1.5 billion by 2011, if it works – but it is a big "if."
The failure of Pfizer's torcetrapib and AtheroGenics's AGI-1067, which the U.S. biotech firm was working on with AstraZeneca Plc, has shaken confidence in the ability of firms to get new heart drugs to market.
It also means there are no short cuts for experimental drugs like darapladib, which is designed to offer something above and beyond the statin class of cholesterol-fighting treatments.
As a result, Glaxo has a high-risk but potentially high-reward product on its books, industry analysts believe. The drug is not expected to win approval until after 2010 but, if it succeeds, it could face few if any direct competitors.
Tackling Inflammation
AGI-1067, which failed in a pivotal Phase III study last month, was the most advanced experimental drug to address the inflammatory processes behind heart disease.
Doctors have for years looked at simply lowering levels of "bad" LDL cholesterol in order to prevent atherosclerosis, or clogging of arteries, but there is growing recognition that inflammation also plays a key role.
Glaxo's darapladib and Decode Genetics’s veliflapon are the only other anti-inflammatory heart medicines in late-stage development, and testing of Decode's product is on hold due to manufacturing problems.
Dr Albert Hofman of the Erasmus Medical Center in Rotterdam, an expert in the links between Lp-PLA2 and heart attacks and strokes, believes Glaxo's approach makes sense.
"I think Lp-PLA2 is a good candidate, though that is obviously by no means settled," he told Reuters.
Lp-PLA2 is already approved as a cardiovascular risk marker in the United States and a diagnostic test for measuring the enzyme is sold by privately owned DiaDexus.
Hofman says scientific evidence is now needed to prove that inhibiting Lp-PLA2 in the body produces clinical benefits.
That question should start to be answered by the results of a dose-ranging study and, more importantly, an imaging study in the second half of 2007, which will assess the impact of darapladib on arterial plaque by peering inside blood vessels.
"That type of evidence will be crucial," Hofman said.
Outcome Studies
At one stage, Glaxo had hoped it might be able to seek marketing approval for darapladib based simply on results of intravascular ultrasound, or IVUS, imaging.
But the experience of torcetrapib, which was scrapped after late-stage tests revealed a link to serious adverse cardiac events, means regulators are virtually certain to require long-term clinical outcome trials, analysts believe.
That will push commercialisation into the next decade, by which time Pfizer's hugely successful statin Lipitor – the world's best-selling medicine -- may face generic rivals.
The prospect of stiff competition from cheap generic forms of Lipitor is another factor Glaxo will have to build into calculations as to the commercial viability of darapladib.
At the moment, many analysts are not building sales of darapladib into their estimates since it is still years away from the market and its efficacy remains unproven.
But success in this year's imaging study could change that, according to Gbola Amusa, an analyst at Sanford Bernstein who is a "bull" of Glaxo stock.
Glaxo shares trade on 13 times forecast 2008 earnings, according to Reuters data, below the European sector average of 14.8, due to worries about future growth of top-selling asthma drug Advair and diabetes drug Avandia, coupled with caution about its future drug pipeline.
Amusa believes darapladib could make give a significant boost to Glaxo's annual sales, which reached 23.2 billion pounds ($45.8 billion) last year, led by Advair which brought in 3.3 billion.
"If this unclogs arteries -- and it's a big 'if' -- that's the type of drug that could sell anywhere from $2 billion to $10 billion," he said.
"And even though Glaxo will have to run outcome studies that will take some years to perform, people will know that if this drug works the potential will be very, very large."