Researchers have overestimated the ability to administer Eli Lilly's experimental prasugrel blood thinner without causing dangerous bleeding, a prominent cardiologist said on Monday.
US regulators in recent months have twice delayed a decision on whether to approve prasugrel, a blood clot preventer being developed in partnership with Daiichi Sankyo that would compete with Bristol-Myers Squibb's Plavix.
Prasugrel proved far better able than Plavix to prevent dangerous blood clots in a large trial called Triton whose results were unveiled last year
But it was associated with a far higher degree of serious bleeding than Plavix, raising concern whether the US FDA would deem its potential benefits worth the risks.
The Triton study involved patients who underwent angioplasties to clear clogged coronary arteries.
Researchers of the Lilly-sponsored trial had theorised that prasugrel could be safely given, as long as it was not taken by three groups shown to have the highest bleeding risk in the trial: patients weighing less than 130lb, those aged 75 or older, or those who had previous strokes or so-called mini-strokes.
But Dr Sanjay Kaul, a cardiologist with Cedars-Sinai Heart Institute in Los Angeles, said on Monday that theory was at odds with scientific facts.
"The investigator analysis is off target because they could not draw the conclusion, based on the data, that bleeding risk is higher in these (supposed) high-risk patients," said Kaul, who is making several presentations on prasugrel at the annual scientific meeting of the American Heart Association.
Kaul specialises in analysing results of published trials.
Kaul said the risk of serious bleeding in the supposedly high-risk patients was 42% higher than with Plavix, compared with 24% higher risk among other patients receiving prasugrel.
Although the bleeding risk for the "high-risk" groups was numerically higher than for the "non-high risk" patients taking prasugrel, it was not statistically significant, he said in an interview.
"So you cannot identify which patients should be excluded," he said, or which ones are at greater or lesser bleeding risk.
Anthony Ware, head of Lilly's cardiovascular programme, said Kaul's statistical method was different from the pre-specified method used by the Triton researchers.
"The highest-risk groups were identified with statistical significance, using Triton's own statistical formula," Ware said. "We would argue that the overall study shows an exciting benefit to risk, including all these groups."
He noted Lilly was in "productive and collegial" discussions with US and European regulators as they continue to weigh prasugrel's approval.
In Triton, prasugrel was 19% more effective than Plavix in preventing cardiovascular death, non-fatal heart attacks and strokes. But it was 32% more likely to cause serious bleeding.
Kaul said the negative bleeding findings should not have been a great surprise because worrisome bleeding risks were seen in an earlier and smaller pilot study of prasugrel.
"That should have caused a red flag," said Kaul, who speculated the FDA could delay prasugrel's approval for several years until Lilly completes another large prasugrel study that is underway.
But he said the agency would likely approve the drug relatively soon if Lilly can provide the agency data showing prasugrel is still effective but safer at a lower dose than the one used in the Triton study.
"This is a good drug but we need to be able to identify the maximum benefits of the drug and to come up with innovative ways to minimise the risk of bleeding," said Kaul.
Even if approved, however, Kaul predicted prasugrel is likely to be a "niche" product.
"I don't think it will be widely used, based on the bleeding concerns," Kaul said, predicting that aspirin and Plavix will remain treatments of choice.
By Ransdell Pierson, Reuters.
