FDA Allows Pediatric Trials for Drug with Risk of Liver Failure
In April 2001, a FDA panel recommended 7 to 3 to approve the Sanofi-Aventis drug Ketek (telithromycin) for streptococcus pneumonia, which affects approximately 4 million Americans annually.¹ Since concerns remained over liver toxicity, Aventis conducted "Study 3014" at the request of the FDA, a study that was later found to be fraudulent. Doctors were receiving $400 for each patient they signed up, signatures and patient data were forged, and ninety percent of the participants at one study site did not even receive the drug.²
Even after a report in the Annals of Internal Medicine linked serious liver toxicity to Ketek, the FDA continued to cite Study 3014 in publicly released safety information and stated that "based on the pre-marketing clinical data it appeared that the risk of liver injury with Ketek was similar to that of other marketed antibiotics."³
Ketek was approved in 2004 for treatment of sinusitis, bronchitis and pneumonia.4 In 2006, officials in the Office of Drug Safety (ODS) found 110 cases of liver problems since the 2004 approval of Ketek, including liver failure and four deaths, and recommended that the FDA withdraw Ketek from the market.5 Agency officials also estimated that Ketek caused acute liver failure at about four times the rate of other antibiotics.6
Despite recommendations and warnings from agency scientists, the FDA allowed pediatric trials using children as young as six months to proceed.7 Meanwhile, the FDA ignored congressional requests for administrative files, a briefing, and interviews with special agents investigating the matter. The FDA also failed to provide an April 27, 2006 letter informing staff of their right to speak to and cooperate with Congress.8 Early in June 2006, Sanofi-Aventis finally "paused" pediatric clinical trials of Ketek.9
1. Wire Reports, “Panel clears drug for pneumonia, urges study.” The Dallas Morning News, 3rd ed., April 27, 2001.
2. C. Gibson and B. Ross, “Drug Safety; Safety Questions,” ABC World News Tonight 6:38 PM EST, ABC News Transcripts, June 14, 2006.
3. Ibid., information in letter from http://www.fda.gov/cder/drug/infopage/telithromycin/qa.htm.
4. Associated Press, “FDA approves new antibiotic; Ketek added to medical arsenal to fight pneumonia,” The Houston Chronicle, April 2, 2004.
5. G. Harris, “Halt is Urged for Trials of Antibiotic in Children,” New York Times, June 8, 2006.
6. Ibid
7. Ibid.
8. “FDA Finally Cooperates With Grassley’s Ketek Review.” Drug Industry Daily, Vol. 5 No. 100, May 22, 2006.
9. “Sanofi-aventis Announces Update to Ketek ® (Telithromycin) U.S. Prescribing Information.” PR Newswire US, 29 June 2006.
