Researchers have overestimated the ability to administer the experimental drug without causing dangerous bleeding, according to a prominent cardiologist, Reuters writes. Prasugrel, you may recall, has twice been delayed by the FDA, which is reportedly set to hold an advisory meeting early next year.

Prasugrel is closely watched because of its blockbuster potential, although the repeated delays also symbolize the FDA’s recent caution. Lilly submitted prasugrel last December and the FDA designated a six-month priority review in February. At the end of June, FDA extended the review by another three months due to extra info given the agency. Then, the FDA missed the September 26 deadline (back story).

In a closely watched clinical trial released last year, Prasugrel surpassed Plavix in preventing dangerous blood clots, but the blood thinner was also yielded a higher incidence of serious bleeding than Plavix, which is marketed by Bristol-Myers Squibb and Sanofi-Aventis. The Triton trial involved patients who underwent angioplasties to clear clogged coronary arteries (look here for more).

Lilly and the Triton researchers suggested Prasugrel could be given safely, as long as it was not taken by three groups shown to have the highest bleeding risk in the trial: patients weighing less than 130 pounds, those aged 75 or older, or those who had previous strokes or so-called mini-strokes, Reuters reminds us.

But Sanjay Kaul, a cardiologist with Cedars-Sinai Heart Institute in Los Angeles, believes 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) hi-risk patients,” he tells Reuters.

He says the risk of serious bleeding in the supposedly high-risk patients was 42 percent higher than with Plavix, compared with 24 percent 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 tells the news service.

“So you cannot identify which patients should be excluded,” he said, adding that too few patients were tested in Triton to draw any firm conclusions about which groups were at greater or lesser bleeding risk.

In Triton, Prasugrel was 19 percent more effective than Plavix in preventing cardiovascular death, nonfatal heart attacks and strokes. But it was 32 percent more likely to cause serious bleeding. Kaul believes 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. Yet he says the FDA would likely approve the drug relatively soon if Lilly can provide 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 minimize the risk of bleeding,” said Kaul. Even if Prasurgrel wins approval, he predicts the blood thinner is likely to be a “niche” product. “I don’t think it will be widely used, based on the bleeding concerns,” Kaul says, adding that aspirin and Plavix will remain treatments of choice.

Source: Reuters