U.S. panel to weigh safety of AstraZeneca's Crestor

WASHINGTON , 12 dec 2009 – U.S. regulators see benefits to using an AstraZeneca Plc cholesterol drug in a vast new group of patients but will ask outside advisers to probe various safety issues, documents released on Friday said.

AstraZeneca wants permission to promote the drug, Crestor, for preventing heart disease in people with normal cholesterol levels but other risk factors based on findings of a large study known as Jupiter.

A Food and Drug Administration reviewer, commenting on a higher number of diabetes cases reported with Crestor patients, said that, at the current time, the benefits seen in the Jupiter trial "outweigh the risk, but further clinical trials are needed to further define this benefit/risk ratio."

The Jupiter trial "was relatively short in duration" and "therefore the long-term complications are unknown," the reviewer said.

The reviewer also said the agency felt it was a "chance finding" that gastrointestinal-related deaths were higher in Crestor patients compared with a placebo.

The comments were included in documents the FDA released ahead of a meeting on Tuesday of a panel of outside advisers.

The advisory panel will be asked to comment on the diabetes and gastrointestinal findings before deciding whether to recommend approval for expanded use, according to a November 12 memo. The FDA also will seek input on a higher number of patients who reported a "confusional state" in the Crestor group, the memo said.

Barclays Capital analyst Brian Bourdot said he expects the advisory panel to support wider use of Crestor.

"Overall, the FDA review appears benign, with few safety concerns and little disagreement that Crestor shows a significant benefit" in the expanded group, Bourdot said in a note to clients.

The Jupiter study showed Crestor cut deaths, heart attacks and strokes in middle-aged people with healthy cholesterol, but elevated levels of C-reactive protein, which is associated with heart disease.

The FDA said it would ask the advisory panel to "keep in mind that an estimated 6 million middle-aged and older men and women in the United States" meet the criteria of people in the study.

AstraZeneca said in an analysis also released by the FDA that Crestor's risks in the Jupiter study were "consistent with the known safety profile." The company said potential side effects were outweighed by the benefits, including a 44 percent reduction in cardiovascular-related deaths, strokes, heart attacks and other problems.

An expanded label for Crestor would boost sales of the drug in the coming years, but industry analysts say the size of the opportunity is uncertain because of the looming arrival of generic versions of Pfizer Inc's Lipitor in late 2011.

Gbola Amusa of UBS believes the Jupiter results could expand the overall statin market by 20 percent to 50 percent in volume terms, lifting AstraZeneca's Crestor sales to some $8 billion in 2012 from $3.6 billion last year.

Others are more cautious, and the consensus forecast for 2012 is $6.75 billion, rising to $6.92 billion in 2013, according to Thomson Pharma.

AstraZeneca's partner Shionogi & Co Ltd also sells Crestor in Japan and recorded $172 million in revenue from the drug in 2008.

The dramatic reduction in heart attack risk seen in Jupiter already has helped boost prescriptions for Crestor since details were unveiled in November last year.

The FDA will make the final decision on whether to allow AstraZeneca to promote Crestor more widely, but it usually follows panel recommendations.

Crestor is a key driver for AstraZeneca as other drugs go off patent, but its exclusivity through to 2016 is being challenged by generic manufacturers in a case due to go to trial in February 2010. AstraZeneca has requested a summary judgment ahead of the trial to eliminate the most significant issue in the case and is awaiting the judge's decision.