The US Food and Drug Administration is under pressure from politicians in the USA who claim that it should not have approved Sanofi-Aventis’ antibiotic Ketek in April 2004 because the data supporting its application was flawed.

They claim that the Food and Drug Administration was wrong to approve the drug because a major safety trial of Ketek (telithromycin) had ‘data integrity problems’.

Ketek had a long and rocky road to the US market, and was turned down by the FDA in both 2001 and 2003 after the agency asked for more information about its safety. The drug’s side effects also re-emerged as an issue on both sides of the Atlantic as recently as January 2006, when the FDA and European Medicines Agency both asked for stronger labeling to warn of serious liver injury associated with the antibiotic’s use.

Ketek was originally filed with the FDA in 2000, and was deemed approvable in June 2001, although the firm was asked to conduct an additional safety study after concerns over liver toxicity, abnormal heart rhythm and visual disturbances. This study, known as 3014, is the subject of the lawmakers’ probe.

After a second request for more data in 2003, Ketek was finally approved in April 2004, with labelling that mentions liver toxicity as a potential side effect.

The politicians – Republican Senator Charles Grassley and Democrat Representatives Edward Markey and Henry Waxman – say there should be an investigation by Congress into the FDA’s approval process for Ketek

In a letter to FDA Commissioner Andrew von Eschenbach, Grassley asks for a probe into claims that the agency’s investigators uncovered discrepancies that led to one of the clinical investigators in the trial being jailed.

The FDA’s Division of Scientific Investigations and Office of Criminal Investigation both investigated study 3014, he notes, and the DSI determined in March 2004 that the study had ‘multiple instances of fraud’ and that ‘the integrity of data from all sites involved in [the] study ... cannot be assured with any degree of confidence’.

With the results of 3014 in question, the FDA should not have approved Ketek, and moreover should have taken action against the drug’s developer.

Sanofi-Aventis has not reported Ketek sales since the third quarter of 2005, when it posted a 7.3% decline in turnover to 38 million euros ($47m) year-on-year, and the antibiotic is a minor product for the company despite once-touted as a potential blockbuster.

But the actions place further pressure on the FDA, which is already under the cosh having been found to lack ‘clear and effective processes’ for monitoring drug safety once medicines are on the market in a recent General Accounting Office report.