AstraZeneca Questions Reliability Of Crestor Adverse Event Reports
This article was originally published in The Pink Sheet Daily
Executive Summary
A Public Citizen petition seeking withdrawal of rosuvastatin is “based on inappropriate and misleading interpretations of selective and incomplete data,” CEO McKillop says. AstraZeneca asserts Crestor’s adverse event profile is similar to other statins.
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Adverse event reports are unreliable sources of information on a product's safety profile, AstraZeneca says in response to a Public Citizen petition seeking withdrawal of Crestor from the market. Public Citizen Health Research Group "incorrectly assumes every spontaneous adverse event report is accurate and reliable evidence that the reported event occurred and was caused by Crestor. This assumption ignores the FDA's express precautions regarding the use of such reports," AstraZeneca said in a July 20 1 response to the agency. HRG filed a citizen petition in March requesting that FDA pull rosuvastatin off the market based on 22 new cases of post-marketing adverse reactions in the U.S., U.K. and Canada (2 (Also see "AstraZeneca Crestor Should Be Withdrawn For Safety Reasons, Public Citizen Says" - Pink Sheet, 4 Mar, 2004.)). In June, the group asserted that 18 cases of rhabdomyolysis had been reported to FDA as of mid-April, with 20 more cases reported since that time (3 (Also see "Crestor Safety Data Under FDA Review; 11 Reports Of Rhabdomyolysis At 10 Mg Dose" - Pink Sheet, 24 Jun, 2004.)). AstraZeneca cautions against relying too heavily on adverse event reports, which the company said have "significant limitations" and are "misused" by HRG. "Safety signals" from adverse event reports "are hypothesis-generating and generally require further investigation that, in turn, may or may not lead to the conclusion that the events were product related," the company's response states. The Public Citizen petition is based on "raw data that's being reported. When you follow up many of these cases, they come out not to be related to the drug," AstraZeneca CEO Tom McKillop said during an earnings call July 22. "The allegations are based on inappropriate and misleading interpretations of selective and incomplete data," McKillop declared. Crestor post-marketing adverse event rates are similar to rates seen in pre-marketing clinical trials and comparable to rates for other statins, AstraZeneca maintained. With post-marketing experience in more than 2 mil. patients with over 6.5 mil. prescriptions dispensed, "the safety profile of Crestor remains consistent with the pre-approval experience as reflected in Crestor's prescribing information," AstraZeneca said. "The overall incidence of adverse events reported with Crestor was similar to placebo" in pre-marketing clinical trials. Crestor adverse event reports may have been incited by adverse publicity, AstraZeneca said. In addition, events are more likely to be reported in the first two years of marketing a product, the company points out. "Despite the increased attention and publicity surrounding Crestor, its adverse event reporting experience has been stable and in line with that of the other currently marketed statins." "FDA has previously warned that accurate evaluations of drug safety cannot be drawn solely from adverse event reports, and rightfully has criticized HRG in the past for using these reports in this fashion, noting that HRG 'ignored all of the well-known limitations to use of FDA spontaneous reports,'" AstraZeneca said. Crestor's share of new prescriptions in the U.S. was 6.8% in the week ending July 9, down from prior weeks as a consequence of Public Citizen's "unfounded challenge on Crestor safety," McKillop said. Crestor sales were $336 mil. in the first half, with $207 mil. coming in the second quarter, AstraZeneca said. Second quarter sales were $113 mil. in the U.S. and $94 mil. internationally, "boosted by the excellent launches in France and Italy," McKillop said. - Benjamin Lum, Lee Kalowski |