FDA approval of bedaquiline — the benefit–risk balance for drug-resistant tuberculosis

Bedaquiline was approved by the Food and Drug Administration (FDA) at the end of 2012 for the treatment of adults with multidrug-resistant pulmonary tuberculosis for whom an effective treatment regimen is not otherwise available (1). One complexity facing the FDA in reviewing the bedaquiline marketing application was that in one of the phase 2 studies, there were more deaths among patients who had bedaquiline added to a background antimycobacterial drug regimen than among those who had placebo added to the same regimen, despite relatively clear evidence of bedaquiline's efficacy in clearing Mycobacterium tuberculosis from sputum. Given this imbalance in mortality, the approval of bedaquiline has appeared paradoxical to some (2). But marketing applications that are reviewed by the FDA often rely on complex risk–benefit evaluations. (The 120-week final results of the aforementioned phase 2 study are reported by Diacon et al. in this issue of the Journal [pages 723–732]; the marketing application, however, contained only efficacy data that were available at week 72.)