Experts say Astra drug's U.S. miss likely a fluke

By Ben Hirschler LONDON, Nov 3 (Reuters) - The failure of AstraZeneca's experimental blood-thinning drug Brilinta to benefit North American patients in a clinical study is most likely a statistical fluke, two of the trial's investigators said. While an interaction with high doses of aspirin cannot be ruled out, Lars Wallentin of Uppsala Clinical Research Centre in Sweden and Richard Becker of Duke University in North Carolina said there were no obvious biological explanations for it. "The most likely explanation is a play of chance, but we still cannot completely get away from (the possibility) that the higher aspirin dose that was used only in the U.S. might have played a role here," lead investigator Wallentin said in a telephone interview. Concerns that high-dose aspirin might interfere with Brilinta were sparked last week when AstraZeneca said researchers were investigating "a possible association". Brilinta -- a rival to Sanofi-Aventis and Bristol-Myers Squibb's $9 billion-a-year seller Plavix -- is one of AstraZeneca's biggest new drug hopes. It showed impressive overall superiority to Plavix in an 18,000-patient study known as PLATO, but its failure to prove itself in the North American sub-group -- accounting for some 9 percent of patients -- has been a puzzle since results were released in August. One difference between North American patients and those elsewhere is that U.S. heart doctors often use a much higher 325-milligram dose of aspirin than in other countries when patients get a stent, leading to the interaction hypothesis. But Wallentin said investigators had not seen any supporting evidence for a difference, with platelet inhibition levels similar and dyspnoea -- a shortness of breath linked to Brilinta -- actually higher in the high-dose aspirin group, suggesting more of an effect from Brilinta rather than less. AstraZeneca filed last month for a licence for Brilinta in Europe and plans to file in the U.S. by the end of the year. Some industry analysts fear the U.S. Food and Administration may delay approval of Brilinta because of the possible aspirin interaction, or even request new studies -- though Becker said he thought this unlikely. "Based on our understanding of sub-group analyses, it's most likely a play of chance," he told Reuters. "Will the FDA come forward and say 'Gee, you should do additional studies with different doses of aspirin'? I don't believe that they will. "I believe that were the drug to be approved it would say that it was tested in combination with aspirin and on the totality of information 75 to 100 milligrams of aspirin may be adequate." (Editing by Elaine Hardcastle) Keywords: ASTRAZENECA BRILINTA/ ([e-mail]; Tel: [phone]; Reuters Messaging: [e-mail]; www.twitter.com/reutersBenHir) COPYRIGHT Copyright Thomson Reuters 2009. All rights reserved.

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