Introduction

On 9 July 2001, the European Commission granted Aventis Pharma a marketing authorization for Ketek for treatment of the following infections: mild to moderate community-acquired pneumonia (CAP), acute exacerbation of chronic bronchitis (AECB), and acute sinusitis (ABS) in patients of 18 years and older, as well as tonsillitis/pharyngitis caused by Streptococcus pyogenes in adults and adolescents, as an alternative when beta-lactam antibiotics are not appropriate.

Throughout the year 2006, the CHMP reviewed relevant safety data on Ketek and asked the Marketing Authorisation Holder to submit comprehensive safety reviews, including updated analysis on hepatic adverse reactions, a review of the benefit-risk balance in each of the therapeutic indications and comparative data from clinical trials with telithromycin compared to other antibiotics. On the 12 February 2007, FDA authorised a new Ketek labelling (i.e. removal of the indications ABS and AECB from the labelling, and an update of safety parts including a contraindication in myasthenia gravis). During the January 2007, these concerns were discussed at CHMP and a request for comparative data from the MAH holder to EMA was made.

Compared to other macrolides, Ketek seems to be associated with a somewhat different risk profile, i.e. adverse reactions as eye disorders, which sometimes are of severe nature, and serious adverse reactions as aggravation of myasthenia gravis, loss of consciousness and acute liver failure. Altogether, these adverse reactions constitute a significant risk which could have impact on the approved therapeutic indications.

Currently registered treatments by indication are:

• 1.CAP: Amoxicillin, Clarithromycin, Trovafloxacin,

• 2.AECB: Amoxicillin-clavulanic acid, Cefuroxime, Clarithromycin, Azithromycin

• 3.ABS: amoxicillin-clavulanic acid, and cefuroxime.

• 4.TP: Penicillin, clarithromycin.

The objective of this case study is to assess the feasibility and suitability of selected approaches for benefit-risk assessment of drugs by the regulator, using Ketek antibiotic as an example. The selected benefit risk methods will be tested using data available from the EMA/CHMP EPAR product information and scientific discussion, 2007.

Two potentially interesting questions in this case study are:

• 1.Should Ketek be given marketing approval at the time of first registration?

• 2.Is FDA justified in removing the indications ABS and AECB from the labeling in 2007

The full report on Telithromycin Case Study can be downloaded in full.