FDA panel votes to recommend approval of new indication for rosuvastatin

Panel recommended use in patients with LDL less than 130 mg/dL and high sensitivity assay C-reactive protein levels at or above 2 mg/L.

An advisory committee to the FDA recommended approval of a supplemental new drug application for an additional indication for rosuvastatin based on results from the JUPITER trial.

The Endocrinologic and Metabolic Drugs Advisory Committee voted 12 to 4 (with one abstaining) to recommend approval of rosuvastatin calcium tablets (Crestor, AstraZeneca) for the additional indication of primary prevention of cardiovascular disease in low-risk and moderate-risk patients with LDL <130 mg/dL and high-sensitivity assay C-reactive protein ≥2 mg/L.

The panel examined data collected from the 17,802-patient JUPITER trial. The JUPITER researchers randomly assigned patients at elevated risk for CVD to receive either 20 mg rosuvastatin daily (n=8,901) or placebo (n=8,901). The reported trial results suggested that the occurrence of the combined primary study endpoint of CV death, stroke, MI, unstable angina or arterial revascularization was lower in the rosuvastatin group vs. placebo (1.6% vs. 2.8%, P<.001). There was also a reduction in total mortality in the rosuvastatin group vs. placebo (2.2% vs. 2.8%, P=.021) and a reduction in venous thromboembolism (0.3% vs. 0.5%, P=.018). There was also an increase in investigator-reported diabetes in the rosuvastatin group vs. placebo (2.8% vs. 2.3%, P=.015).

“I voted yes, and I am concerned with the ethical issue of denying the majority of the population a beneficial therapy that, in the event that this supplemental new drug application is not approved, would cause the drug to continue to be used off-label for that indication,” said William Hiatt, MD, president of the Colorado Prevention Center and professor of medicine at the University of Colorado Denver School of Medicine. “Defining the population that would be appropriate for extended use of this statin drug needs to be carefully portrayed on the labeling and in the marketing materials.”

Some of the panelists who voted against recommending approval were concerned with the specific indication of use of the drug in patients with C-reactive protein ≥2 mg/L, as well as the increase in diabetes observed in the rosuvastatin group.

“These emerging risk factors should not be included individually. The United States Preventive Task Force noted that for an individual risk factor to be included individually it has to be reliable and an accurate measurement,” Kenneth Burman, MD, panel chair and chief of the endocrine section at Washington Hospital Center in Washington, DC, said of his vote against recommendation at the meeting. “It should be an independent predictor of CV risk in patients without known CVD.” – by Eric Raible