Safety fears halt paediatric trials of Ketek

Sanofi-Aventis has halted recruitment to clinical trials of its antibiotic Ketek (telithromycin) in children worldwide following discussions with the US Food and Drug Administration (FDA) about "possible serious adverse effects".

The first member of a new class of antibiotics known as ketolides, the drug was being tested in a new paediatric indication for the treatment of upper and lower respiratory tract infections (RTIs), including acute bacterial sinusitis and acute exacerbation of chronic bronchitis. According to a company spokesman, recruitment of new patients has been halted in order to "review the evaluation of Ketek's benefit-risk profile".

The trials, which began in mid-2005 in more than a dozen countries, have been carried out on around 1,100 patients with ear infections and tonsillitis. The relatively short duration of the treatment period means that the cessation of recruitment effectively amounts to ending the trials. They were expected to include a total of 4,000 children and the company had been anticipating a 2007-8 filing for the drug in the new indication.

In January 2006, "Annals of Internal Medicine" published an article featuring three reports of "serious adverse events", in three patients taking Ketek. The patients - aged 46, 51 and 26 - experienced jaundice and abnormal liver function. They recovered, required a transplant and died respectively. All three had previously been healthy.

According to the FDA, pre-marketing clinical data showed the risk of liver injury to be "similar to that of other marketed antibiotics", and two advisory committee meetings concluded that the risk for hepatotoxicity from Ketek was similar to that from approved antibiotics Augmentin and erythromycin.

However, the FDA and Sanofi are now discussing possible label modifications for Ketek in adults to include warning of liver damage risks. The European Medicines Agency (EMEA) asked for similar modifications at the end of January.