Tuberculosis

Series

Tuberculosis 5 Global tuberculosis drug development pipeline: the need and the reality
Zhenkun Ma, Christian Lienhardt, Helen McIlleron, Andrew J Nunn, Xiexiu Wang
Lancet 2010; 375: 2100–09 Published Online May 19, 2010 DOI:10.1016/S01406736(10)60359-9 This is the fifth in a Series of eight papers about tuberculosis Global Alliance for TB Drug Development, New York, NY, USA (Z Ma PhD);Stop TB Partnership Secretariat, Stop TB Department, WHO, Geneva, Switzerland (C Lienhardt PhD); Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa (H McIlleron PhD); Medical Research Council Clinical Trials Unit, London, UK (Prof A J Nunn MSc); and Tianjin Centres for Disease Control and Prevention, Tianjin, China (Prof X Wang MD)Correspondence to: Dr Zhenkun Ma, Global Alliance for TB Drug Development, 40 Wall Street, New York, NY 10005, USA zhenkun.ma@tballiance.org

Drugs for tuberculosis are inadequate to address the many inherent and emerging challenges of treatment. In the past decade, ten compounds have progressed into the clinical development pipeline, including six new compounds specifically developed for tuberculosis.Despite this progress, the global drug pipeline for tuberculosis is still insufficient to address the unmet needs of treatment. Additional and sustainable efforts, and funding are needed to further improve the pipeline. The key challenges in the development of new treatments are the needs for novel drug combinations, new trial designs, studies in paediatric populations, increased clinical trialcapacity, clear regulatory guidelines, and biomarkers for prediction of long-term outcome. Despite substantial progress in efforts to control tuberculosis, the global burden of this disease remains high. To eliminate tuberculosis as a public health concern by 2050, all responsible parties need to work together to strengthen the global antituberculosis drug pipeline and support the development of newantituberculosis drug regimens.

Introduction
Rifampicin, discovered 40 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class are part of a 6-month, regimen that is ineffective against multidrugresistant (MDR) and extensively drug-resistant (XDR) tuberculosis, and are difficult to use with many antiretroviral drugs. Tencompounds have progressed to the clinical development pipeline for the treatment of tuberculosis. These compounds, if properly developed, have the potential to become part of a future regimen that could greatly affect the global tuberculosis control effort. The potential benefits of new drugs in development were investigated in a modelling study.1 The results of this study suggest that the combinationof a 2-month

treatment regimen that cures 95% of MDR tuberculosis, a generalised nucleic acid amplification test, and a joint pre-exposure and post-exposure vaccine could potentially reduce the incidence of this disease by 71% by 2050.1 The combination of preventive treatment for latent tuberculosis infection and a 2-month drug regimen might reduce incidence by 94%.1 In this review, we discussthe unmet needs in the treatment of tuberculosis, the global pipeline of new compounds that are in clinical development, and draw attention to the challenges in drug research and development. Issues associated with vaccines and diagnostic tests are reviewed in other reports in The Lancet Series about tuberculosis.2,3

Search strategy and selection criteria Key messages • Drugs for tuberculosisare inadequate to address the many inherent and emerging challenges of treatment. Development of new technology for biomedical intervention should be a top priority of the global tuberculosis control and elimination agenda. • Substantial progress has been made in development of new drugs during the past decade, with ten compounds progressing through the clinical development pipeline, including six...