The antiplatelet drug is being geared up to take on Plavix (clopidogrel), a $5.8bn (€4bn) monster marketed by Sanofi-Aventis and Bristol-Myers Squibb (BMS), but the latest clinical trial data has somewhat blunted the newcomer's claws.

After a large Phase III trial, Lilly and its Japanese partner Daiichi Sankyo found that prasugrel does indeed reduce the chance of having a heart attack compared to Plavix, but this improvement comes only at the cost of an increased risk of fatal bleeding.

Dr John Alexander, head of R&D at Daiichi Sankyo, called the results "promising" and said the two companies are "expeditiously finalising our submission package and are still hopeful to submit to the [US Food and Drug Administration] FDA by year end."

Lilly desperately needs this drug to succeed: the firm is set to lose over 50 per cent of its revenue to generics by 2012, according to the latest data from Moody's, and prasugrel was seen as one of the best hopes it had of staving off some of this loss.

Both Plavix and prasugrel are thienopyridine molecules that act as prodrugs - they need to be metabolised to an active form before they have a therapeutic affect - in this case before binding to the adenosine diphosphate (ADP) P2Y

receptor to prevent platelets from forming.

The primary efficacy end point of the Phase III trial comparing the two was death from cardiovascular causes, nonfatal heart attack (myocardial infarction), or nonfatal stroke. Only 9.9 per cent of patients on prasugrel reached one of these three end points, compared to 12.1 per cent of patients on Plavix. This was largely down to the fact that 7.4 per cent of prasugrel patients suffered from a heart attack, compared to 9.7 per cent with Plavix.

There was no significant difference between the two treatment groups in the rate of stroke or of death from cardiovascular causes not preceded by recurrent myocardial infarction

However, major bleeding was observed in 2.4% of patients receiving prasugrel and only 1.8% of patients receiving Plavix - with 0.4 per cent of patients suffering fatal bleeding with Lilly's drug, in contrast to only 0.1 per cent of those on Plavix.

The mixed results were not entirely unexpected as they come only two weeks after the companies suspended enrolment in two Phase II trails of prasugrel until the protocol could eb amended. The move left investors and analysts waiting for these Phase III results with baited breath, as they were likely to indicate what was the problem in the halted Phase II trials. And so it has proved.

Put simply, for every 1,000 people treated with prasugrel compared to Plavix in the study, there were 23 fewer heart attacks but an additional six major bleeding complications. The risk of bleeding was particularly high in patients over 75, those who weighed less than 60 kg and those with a prior history of transient ischemic attack (TIA) or stroke.

The fact that the side-effects can be linked to certain high-risk patient subsets is crucial to Lilly and Daiichi Sankyo as it will allow them to argue that as long as these patients are avoided, plasugrel could still be used. Whether or not the FDA agrees remains to be seen, however, especially given that the regulators are becoming increasingly cautious in approving new drugs.

If this data doesn't convince the FDA, perhaps the next set will prove more palatable. The two companies have announced a large new Phase III trial will begin next year, again testing prasugrel against Plavix, but this time in patients with a group of common heart conditions, including unstable angina (chest pain) and heart attacks.

"Irrespective, we believe its commercial potential is minimal," Reuters quote Morgan Stanley analyst Andrew Baum as saying in a research note.

Other analysts also reduced their forecasts for the drug. Over at Sanford Bernstein, Tim Anderson cut his 2012 sales prediction in half to $800m, according to Reuters.

If the drug does eventually make it to market, one thing is for sure - clinicians will face a tough choice on whether to use Plavix or prasugrel.

Source: New England Journal of Medicine (NEJM)

"Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes"

Dr Stephen Wiviott et al. doi 10.1056/NEJMoa0706482