* FDA panel on Brilinta July 28, day before Q2 results
* Market expects positive vote but U.S. data raises doubts
* Lack of benefit in U.S./Canada vs strong overall efficacy
* Shares could fall 10 pct on rejection, gain 5 pct on okay
By Ben Hirschler and Lisa Richwine
LONDON/WASHINGTON, July 23 (Reuters) - U.S. experts studying AstraZeneca’s (AZN.L) new heart drug Brilinta face a dilemma: should a pill with clear overall efficacy be approved, even when it fails to show a benefit in North America?
Many analysts think the answer is “yes” and that Brilinta, for preventing heart attacks, will be waved through because the regional anomaly may just be a statistical fluke from a relatively small subset analysis.
But it is clear AstraZeneca’s biggest new drug hope faces tough questions when a Food and Drug Administration advisory panel reviews it on July 28. The day-long meeting is likely to overshadow second-quarter results on July 29, when some analysts believe AstraZeneca could announce an increased share buyback.
Ira Loss, an analyst who follows the FDA for Washington Analysis, said the lack of benefit seen in North American patients in a pivotal study should not bar approval.
“It’s an established precedent that there are drugs on the market that have this anomaly and they still get approved,” Loss said. He pointed to AstraZeneca’s Toprol XL as an example.
That drug won FDA clearance for the additional use of congestive heart failure based on a trial which found Toprol XL sharply reduced deaths in patients overall, although U.S. patients saw no advantage.
In that case, the FDA reviewers concluded the results might be due to chance or differences in medical care and patient demographics in various countries, and the agency cleared the new use in light of the strong overall results.
Toprol XL was also helped by data showing a reduction in hospitalisations of U.S. patients that worked in its favour.
Brilinta, though, may be different.
Tim Anderson, an analyst at Sanford Bernstein, believes the FDA is struggling with the North American findings and it remains to be seen how much weight will be given to them.
“If they are weighted heavily and there is felt to be no easy explanation, then Brilinta’s approvability might be at risk,” he said.
With consensus 2014 sales forecasts for Brilinta standing at $1.1 billion, according to Thomson Reuters data, and the drug central to AstraZeneca’s strategy for overcoming patent losses, a lot is riding on next week’s panel.
Deutsche Bank analysts believe the shares could fall as much as 10 percent if there is no recommendation for final approval and gain 5 percent on a positive vote, since the U.S. market represents 70 percent of the Brilinta sales opportunity.
Citigroup puts the downside at 5-7 percent and the upside at 2-5 percent.
In practice, the panel meeting may not provide a definitive answer given the perplexing clinical evidence. The new blood thinner showed impressive overall superiority to Sanofi-Aventis (SASY.PA) and Bristol-Myers Squibb’s (BMY.N) $9 billion-a-year blockbuster Plavix in an 18,000-patient study last August that compared using the two drugs alongside aspirin.
But among the relatively small number of North American patients on Brilinta plus aspirin there was actually a non-significant trend towards a worse outcome.
One possibility is that Brilinta doesn’t work as well when patients get a high dose of aspirin after heart treatment, as is common practice in the United States but not other countries.
Questions about aspirin as well as uncertainties about different doses of Plavix used among some patients might prompt calls for more studies, either before or after approval.
Alternatively, some analysts think the FDA panel could approve Brilinta as a new treatment option but not allow any claims about its cardiovascular benefits.
And the panel, anyway, may not give the final answer. Jefferies analysts suspect the key opinion leaders may vote in favour of approval, with the FDA then asking for more trials before granting a marketing green light. Even it does get to market, Brilinta will face a tough commercial environment. The prize is certainly large -- Plavix, after all, is the world’s second-biggest-selling medicine -- but the Sanofi/Bristol blockbuster is already facing generic rivals in much of Europe and will lose U.S. patent protection in 2012.
Lacklustre demand for Effient, Eli Lilly’s (LLY.N) Plavix challenger, also suggests Brilinta has a fight on its hands. (Editing by Michael Shields)