June 17, 2008 1:13 pm

prasugrel: FDA set to weigh in, high chance for approval with label warnings - cardiologists

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With the FDA set to finally weigh in on Eli Lilly and Daiichi Sankyo’s oral antiplatelet Effient (prasugrel), cardiologists say they are hopeful the drug will be approved and the bleeding risk found during clinical trials will be dealt with in the drug’s labeling.

The drug is set to compete with Plavix (clopidogrel), the blockbuster drug marketed by Bristol-Myers Squibb and Sanofi-Aventis, and the Phase III head-to-head TRITON trial with clopidogrel showed prasugrel to be 19% more efficacious. But that same trial showed prasugrel to have a greater bleeding risk than clopidogrel, prompting concern with cardiologists that the drug could fail to gain approval.

The FDA is expected to rule on approval before the drug’s PDUFA date of 26 June. This news service previously reported that concern over the bleeding risk could lead to a narrow label or black box warning, and cardiologists admitted the risk was too significant to ignore.

Dr Antonio Gotto, dean of Weill Cornell Medical College, said it was his hope as a cardiologist that the FDA would approve the drug and give physicians an added option. “I would favor giving the cardiologists the benefit of the doubt, and let the cardiologists make that decision. Let them have access to it, but with appropriate warnings,” he argued. But he admitted the FDA decision was a difficult one to predict. “I think it will come down to a judgment call on the part of the FDA, whether they think it’s worth it or not. I don’t think it is completely clear cut.”

A spokesperson for Eli Lilly declined to speculate on what the FDA might do with the drug, but said the company was confident the package presented to the agency was strong. The spokesperson also pointed out that prasugrel was granted a priority review by the agency, and that the FDA sets a goal of reaching a decision on 90% of those applications by the target date. This means 10% of priority reviews take longer than the target date indicates.

Dr Eric Bates, a site investigator for the drug and a cardiologist at the University of Michigan, said Eli Lilly could persuasively argue that in a large number of patients the bleeding risk essentially disappears. He pointed out the analysis of the TRITON study that showed the increased bleeding risk was concentrated in patients either over the age of 75, weighing under 60 kilos, or those with a previous neurologic event.

“One could argue, as these guys have, that if you avoid those three subgroups you don’t have an increased bleeding risk and you get increased efficacy,” Bates said. “So it potentially could be an attractive drug for a lot of people.”

There remains more than a slight chance, however, that the agency will take the cautious route and deny the drug’s approval or at least require additional studies be completed, further delaying the drug’s arrival on the market, the cardiologists admitted.

Dr Aaron Berman, a cardiologist at Northpointe Heart Center in Berkeley, Michigan, admitted the bleeding risk was a concern. Still, he believed the drug’s risk-benefit ratio merited approval. “I think most cardiologists would like to see it approved,” he said, but said a black box warning label was a very real possibility. Berman raised another advantage the approval prasugrel might have, pointing out that the high cost of Plavix was hampering treatment and competition may prove beneficial from a price perspective.

Dr Howard Kline, a cardiologist at California Pacific Cardiovascular Group, said that because there have proven to be some treatment-resistant patients with Plavix, the addition of a new drug in the space could provide an option for an additional 15 to 20% of patients. But Kline conceded the FDA could delay any decision on prasugrel, or ask for additional data on the risk involved, which would be seen as a significant setback for Eli Lilly.

Analysts have said the approval of prasugrel is crucial to Eli Lilly, with the company suffering from a thin pipeline and upcoming patent expirations. The company has a market cap of USD 54.64bn.

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