Pipeline of drugs for related diseases

Abstract

For the first time in decades, there are multiple new drugs in the pipeline for the treatment of tuberculosis (TB). In addition, existing drugs are being repurposed or optimized for TB with the goal of shortened treatment duration for drug-sensitive TB and safer, shorter treatments for multidrug-resistant (MDR) TB. In this review, the results of recent trials evaluating novel combination regimens for TB disease and latent TB infection are described. High-dose rifamycins (rifampin and rifapentine) and fluoroquinolones directly observed have treatment-shortening potential when used for drug-sensitive TB disease, and a 12-dose once-weekly regimen of rifapentine along with isoniazid effectively treats latent TB. Bedaquiline, an anti-TB drug with a novel mechanism of action, and delamanid, a nitroimidazole, are entering phase 3 trials. Both improve rates of sputum culture conversion among patients with MDR-TB. Other nitroimidazoles and oxazolidinones are in Phase 2 testing, as are combinations involving multiple new chemical entities. With the resurgence of anti-TB drug discovery efforts, we now have a modestly robust pipeline of new anti-TB drugs. Several promising new regimens involving investigational and existing drugs that may be capable of shortening treatment for drug-sensitive TB and improving management of drug-resistant TB are in late-phase clinical evaluation.