Eagerly-anticipated data from a large late-stage study comparing Eli Lilly and Daiichi Sankyo’s new antithrombotic prasugrel with Sanofi-Aventis/Bristol-Myers Squibb’s blockbuster Plavix appear to have impressed and disappointed observers in equal measure.

Firstly, Lilly noted that results from the 15-month, 13.608-patient TRITON TIMI-38 trial showed that prasugrel produced “a highly significant 19% reduction in relative risk” for the endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke when compared with Plavix (clopidogrel) in the treatment of patients “across the full spectrum of acute coronary syndrome undergoing percutaneous coronary intervention”.

Also, in the important subgroup of patients with diabetes, prasugrel reduced the relative risk of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke by 30% and cut the recurrence of stent thrombosis by 52%. The positive data piled up as the TRITON trial also showed that treatment with prasugrel significantly reduced the relative risk of cardiovascular death, non-fatal heart attack and non-fatal stroke by 21% percent in patients with ST-elevation myocardial infarction and by 18% for those suffering from unstable angina. In addition, prasugrel-treated patients experienced a 34% decline in procedures to reopen blocked arteries and a 42% reduction in heart attack with subsequent death from cardiovascular causes.

All very impressive but then Lilly also noted that prasugrel-treated patients experienced a statistically significant increase in non-coronary artery bypass grafting major bleeding compared to clopidogrel-treated patients (2.4% versus 1.8%, or 146 versus 111 patients), including higher rates of life-threatening bleeding (1.4% compared to 0.9%).

It is the bleeding problem that worried analysts as the results were presented at the American Heart Association’s Scientific Sessions in Orlando, Florida and Tim Anderson, an analyst with Sanford Bernstein said: "I just wonder how many physicians are going to use the drug given the bleeding profile". Other experts suggested that the problem means that the US Food and Drug Administration will demand additional trials before any approval is given.

However others preferred to look on the positive side. Elliott Antman, senior investigator with the TIMI Study Group at Harvard Medical School, said the data “provides compelling evidence that the prasugrel regimen tested is superior to standard dose clopidogrel as an antiplatelet therapy to support patients undergoing coronary stenting". He added that with the data from TRITON and other studies, “we expect to define populations at particular bleeding risk to help establish clear guidance for using this promising therapy”.

Anthony Ware, Lilly’s “cardiovascular platform leader” for the drug, claimed that the data “validate our decision to test prasugrel head to head against clopidogrel” and " help us further tailor prasugrel therapy". Lilly and Daiichi also reiterated their intention hopes to file the drug with the FDA before the end of the year”.

Plavix is expected to come off-patent in the USA in 2011 and if prasugrel is found to be more effective, it could have peak sales of $4 billion and more if Lilly and Daiichi manage to get the drug onto the market before generic clopidogrel is introduced. However investors are wary, given the FDA’s toughening stance when it comes to new approvals, and Lilly’s share price took a jolt last week when a halt was called to enrolment for two “small” Phase II trials of prasugrel as a result of pharmacokinetic analyses which indicate that “a dose adjustment may be appropriate for certain subpopulations”.