UPDATE 4-AstraZeneca stumbles as Brilinta held up in U.S.

* U.S. agency issues complete response letter for heart drug

* Requests further analyses of data but not extra studies

* Brilinta is company’s top new drug hope

* Drug may face around 9-month delay in world’s top market

* AstraZeneca shares fall 5.5 percent

(Adds further analyst quote, latest shares)

By Ben Hirschler

LONDON, Dec 17 (Reuters) - AstraZeneca Plc's AZN.L new heart medicine Brilinta failed to win approval from U.S. regulators, delaying a vital new product designed to rival Plavix, the world's second-biggest selling drug.

The drugmaker said on Friday it had received a so-called complete response letter from the Food and Drug Administration (FDA), requesting further analyses of clinical trial data but not additional studies.

The market had been widely expecting a green light from the FDA by Dec. 16, especially as the deadline for the agency to deliver its verdict had already been postponed once from Sept. 16.

AstraZeneca shares, which had spiked up in recent sessions to reach their highest since late October, went into retreat and were down 5.5 percent at 2,981 pence by 1215 GMT.

“This does emphasise the risks associated with AstraZeneca -- in that if you are dependent upon a small number of products, one issue can have a disproportionate impact on the business,” said Evolution Securities analyst Dominic Valder.

AstraZeneca is relying heavily on revenue from Brilinta -- which has been approved in Europe -- to offset expiring patents on some of its best-selling medicines, such as heartburn treatment Nexium and Seroquel for schizophrenia.

Mark Clark at Deutsche Bank said the setback would delay and reduce confidence in the drug’s potential in the United States, where sales of Brilinta had been expected to contribute some 10 percent to group earnings per share by 2015.

Market forecasters have predicted peak annual sales for Brilinta of $2 billion or more. But with analysts now expecting, at best, a U.S. delay of around nine months, those figures look vulnerable and expectations for 2011 are unlikely to be met.

Current consensus forecasts from Thomson Reuters Pharma point to Brilinta sales of $181 million next year -- a figure that will be hard to reach without early U.S. sales, since most European launches will only occur in the second half of 2011.


The blood thinner is a competitor tor Sanofi-Aventis SASY.PA and Bristol-Myers Squibb's BMY.N Plavix, the world's second-biggest drug, with sales last year of more than $9.5 billion.

The product won a 7-1 vote in its favour from a U.S. advisory panel in July, but a perplexing lack of benefit seen in a North American sub-group of patients in a key clinical trial meant a clear passage through the FDA was never guaranteed.

Tim Anderson, an analyst at Sanford Bernstein, said the FDA likely wanted to probe this issue more by seeking further analyses of data from the company’s main study in Brilinta, known as PLATO.

“This suggests there remains some degree of controversy with the fact that in the U.S. subset of PLATO patients, Brilinta was shown to be worse than Plavix, in contrast to the worldwide dataset that showed Brilinta was better than Plavix,” he said.

AstraZeneca said it remained confident about Brilinta’s prospects in the world’s biggest market and in its ability to respond to the FDA’s questions.

But Jeff Holford of Jefferies said the uncertainty at the FDA raised doubts about Brilinta’s commercial potential.

Brilinta, or Brilique as it will be known in Europe, is designed to prevent dangerous blood clots in patients with serious chest pain or previous heart attacks.

Given the competitive landscape, AstraZeneca officials will have been working hard to ensure it gets the best possible label from U.S. regulators -- something which may have backfired, according to Savvas Neophytou of Panmure Gordon.

“We believe the company has been negotiating strongly on the label and probably pushed it too far, so the agency responded with a request of further analysis,” he said.

As well as competing with Plavix, which is now off patent in parts of Europe and will lose U.S. patent protection in 2012, it is also a rival for Eli Lilly's LLY.N and Daiichi Sankyo's 4568.T recently introduced Effient. Effient has so far had slow sales, due to concerns about bleeding risks.

Plavix, Brilinta and Effient all work by stopping blood platelets from sticking together and forming clots that can cause heart attacks and strokes. (Editing by David Holmes and Hans Peters)