Suggests That Reports Of Acute Liver Failure Support A Ketek Recall
A November 22, 2006 Reuters article by Susan Heavey reports on the latest development as regards the continuing controversy surrounding Ketek (telithromycin), an antibiotic from Sanofi-Aventis. The Reuters article summarizes a letter to the editor of The New England Journal of Medicine (NEJM) written by David Graham, a high-profile FDA staff member who has spoken out often about drug safety issues. David Graham's letter, entitled "Telithromycin and Acute Liver Failure", was published in the November 23, 2006 edition of NEJM, a leading medical journal.
Essentially, Graham takes the FDA to task for the way the agency evaded the recommendation of a 2001 FDA advisory committee which had "voted against the approval of [Ketek] primarily because of concern about hepatotoxicity." In his letter Graham describes the tactic in detail, but the basic point seems to be this:
Lacking reliable data to counter the advisory committee's concern, the FDA took the unprecedented step of requesting post-marketing data from voluntary case reports from Germany and France as proof of the drug's safety, rather than requiring another clinical trial....
The FDA interpreted the absence of a signal of acute liver failure in the overseas data as confirmation of [Ketek]'s safety when the data could not be used to identify the problem. In effect, the FDA's decision in 2004 to approve the use of [Ketek] for acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, and community-acquired pneumonia was made in the absence of reliable data disproving the concern expressed in 2001 by the advisory committee.
According to the November 22 Reuters article, despite these facts, the FDA and the drug company Sanofi-Aventis maintain that the approval of Ketek was done properly and that this antibiotic should remain on the market:
- "FDA spokeswoman Kristen Neese said the agency was aware of the limitations of data gathered after marketing, but it was not uncommon to use such information or reports from other countries. The agency also weighed other data in approving Ketek, she added."
- "Company spokeswoman Lisa Kennedy said Ketek 'has been extensively studied' and that the drugmaker was required to submit all post-marketing data to the FDA."
David Graham, on the other hand, asserts in his November 2006 NEJM letter that the there is a case to be made that Ketek should be recalled for safety reasons:
A recent analysis of the FDA's post-marketing database showed that the rate of reporting of acute liver failure was 3.5 to 11 times as high for [Ketek] as for other antibiotics marketed for similar indications, with a reporting rate of 167 cases of acute liver failure per 1 million person-years of [Ketek] use, as compared with the expected rate of 1 case per 1 million person-years. Without accounting for underreporting (the actual incidence could be 10 times as high), this reporting rate is greater than that for troglitazone or trovafloxacin and is similar to that for bromfenac — three drugs previously removed from the U.S. market by the FDA because of the increased risk of acute liver failure. Given that [Ketek] is neither clinically superior to other drugs prescribed for respiratory tract infections nor uniquely life-saving, physicians, patients, and third-party payers might wish to reconsider their choice of antibiotic for such infections.
As covered previously, in mid-December 2006 the FDA will convene a two-day meeting to consider whether Ketek should remain on the market, or not.
(Posted by: Tom Lamb)