Strong Panel Backing For AstraZeneca Blood Thinner Brilinta

The blood-thinning drug club is one step closer to getting a new member. Today, an FDA advisory panel gave a thumbs-up recommendation to Brilinta (ticagrelor), an experimental blood thinner from AstraZeneca. The vote was 7-1 in favor of approval, an enthusiastic endorsement that increases the chances that FDA will decide to approve the drug. The FDA is supposed to make its call on Brilinta by Sept. 16.

Brilinta is in the same drug class as Plavix (clopidogrel), a blood thinner that’s the second best-selling drug in the world, and a drug that is going off-patent next year. Also in this class of drugs: Effient (prasugrel).

Brilinta’s got the same molecular target as Plavix and Effient- P2Y12, a G-protein-coupled receptor on platelets that responds to the nucleotide adenosine diphosphate. But unlike the other two drugs, Brilinta targets P2Y12 reversibly. That reversibility could come in very handy in the clinic, as is implied in the opening sentences of this paper describing the clinical trial PLATO, which compared Plavix and Brilinta.

Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients.

And it seems that the vote at the FDA panel is a vote of confidence for that mechanism. The most uncertain moments in the meeting had to do with unexpected clinical trial results in U.S. patients. Here’s how Ed Silverman at Pharmalot described it.

The key clinical trial compared Brilinta to Plavix in 18,624 patients in 43 countries who were being treated for a blocked artery or heart attack. The results showed the med reduced heart attacks, strokes and cardiovascular death 16 percent compared with Plavix after a year’s treatment. And all of the patients were given aspirin. But about 9 percent – who were from the US – saw no benefit.

The FDA explained the difference by suggesting the dosage of aspirin given US patients was higher, but there was no clear understanding, as the panel grappled with differing patient treatment methods beyond aspirin dosing.

It’s still not clear what happened in that subset of patients. I’ll be watching this space to see whether more clinical trials pop up.

And a blast-from-the-past bonus: check out C&EN’s own coverage of the medicinal chemistry story behind Brilinta, from back in 2003. (It was called AZD6140 back then.)

Author: Carmen Drahl

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