FDA Confirms Benefits of Crestor in Patients without Elevated Cholesterol

In documents posted online Friday, the Food and Drug Administration cites the findings of AstraZeneca's study released last November. The study showed that patients with lower cholesterol and few heart risks could still benefit from taking Crestor, setting the stage for a dramatic expansion in use of the drug that already exceeds $1 billion in annual sales.

The British drugmaker wants the FDA to broaden Crestor's labeling based on those results.

But the FDA's review also cites several safety concerns, including a higher rate of diabetes in patients taking Crestor.

About 2.8 percent of patients taking Crestor in the 17,000-patient Jupiter study developed diabetes, compared with 2.3 percent of patients taking a dummy pill. The difference was statistically significant, according to the FDA.

But one FDA reviewer suggests that diabetes is a side effect of all drugs in that class, which include Crestor, Pfizer's Lipitor and other cholesterol-lowering pills.

"It is this clinical reviewer's opinion that the treatment benefit observed in the Jupiter trial outweighs the risk, but further clinical trials are needed to further define this benefit-risk ratio," writes the unnamed reviewer.

The FDA on Tuesday will ask a panel of outside experts to weigh in on whether Crestor use should be expanded. The agency is not required to follow the group's advice, though it often does.

The panel also will discuss 13 deaths due to gastrointestinal disorders seen in Crestor patients, compared with just one in the placebo group. The agency review suggests the higher rate was a "chance finding."

The FDA also will raise questions about 18 Crestor patients who reported a "confusional state," compared with four in the placebo group.

AstraZeneca's Jupiter study focused on patients with lower cholesterol and elevated C-reactive protein, a key indicator of inflammation that can lead to clogged arteries. Under current guidelines, those patients are not recommended for treatment with statins, the best-selling class of cholesterol-lowering drugs.

Patients taking Crestor experienced a 44 percent reduction in major heart problems, including heart attack, stroke and death. It's unclear whether the positive results seen in Jupiter were due to lower cholesterol or C-reative protein, since Crestor reduces both.

In its own briefing documents, AstraZeneca points out that half of all heart problems occur in patients with normal cholesterol levels, who stand to benefit from expanded use of Crestor.

Although the agency's Endocrinologic and Metabolic Drugs Advisory Committee agreed that the benefit of rosuvastatin outweighed the risk, it said that patients should be carefully monitored for diabetes and they admonished the manufacturer to "carefully define the target population in marketing materials."

Broader FDA labeling for the drug would expand the potential U.S. market by at least 6 million patients, according to the FDA. Sales of the drug rose 30 percent in the last quarter to $1.15 billion compared with the prior year period.