* 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 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
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)