U.S. FDA staff mixed on AstraZeneca drug

WASHINGTON (Reuters) - U.S. reviewers gave mixed views on AstraZeneca Plc's AZN.L experimental blood thinner but the company's shares rose on investor optimism that an advisory panel will back the potential blockbuster drug.

The main issue facing Brilinta is a lack of benefit for the relatively small number of North American patients in a company study of 18,000 people. That conflicted with a sharp reduction in cardiovascular deaths and heart attacks for patients overall compared with the standard blood thinner Plavix.

AstraZeneca has suggested higher aspirin doses in the United States could account for the differences.

But in documents released on Monday, FDA reviewer Thomas Marciniak said “aspirin dosing does not explain the disparate results” between U.S. patients and other countries.

Other FDA staff, in memos prepared for an advisory panel that meets Wednesday, seemed willing to accept the differences.

Reviewers in the agency’s office of pharmacology recommended Brilinta’s approval with a post-market study “aimed to reconcile the findings” from the United States.

Another FDA reviewer, Dr. Robert Fiorentino, wrote that “it seems difficult to discount outcomes, particularly a benefit in all-cause mortality, observed in over 17,000 subjects” outside the United States.

AstraZeneca shares gained 3.9 percent on the New York Stock Exchange after the FDA documents were released on Monday afternoon.

“The FDA commentary points to a somewhat more positive outcome than expected,” said Viren Mehta, principal at Mehta Partners in New York.

Mehta said some investors had been concerned that the FDA might object that Brilinta was compared with a standard dose of Plavix, rather than a twice-higher dose that has become the “new normal” dose used by many doctors.

The drug would compete directly with Plavix, sold by Sanofi-Aventis SASY.PA and Bristol-Myers Squibb BMY.N, the world's second-best selling drug with annual sales of about $9 billion.


The FDA’s Marciniak said AstraZeneca’s main study of Brilinta was generally well-run but had incomplete follow-up rates that were “concerning.”

“One relevant question, given the incompleteness of follow-up, are the results real?” Marciniak wrote.

He said U.S. patients had “worse results” for all effectiveness measures including heart attacks, strokes and deaths. He added that the “major approvability issues” appear related to effectiveness.

The agency will ask the advisory panel to vote on whether to recommend Brilinta’s approval. The FDA usually follows panel recommendations. A final decision is due by September 16.

AstraZeneca is counting on Brilinta to help offset the looming loss of patent protection on key drugs such as heartburn treatment Nexium and antipsychotic Seroquel.

Consensus 2014 sales forecasts for Brilinta stand at $1.1 billion (700 million pounds), according to Thomson Reuters data. The company’s total sales topped $32 billion in 2009.

“When efficacy and safety were analyzed together, ticagrelor provided a net clinical benefit” over Plavix, AstraZeneca said in a summary prepared for the advisory panel.

Ticagrelor is the generic name for Brilinta.

Reporting by Lisa Richwine; additional reporting by Ransdell Pierson in New York; Editing by Tim Dobbyn