Tuberculosis, a neglected opportunity?

Abstract

Historically, tuberculosis (TB) has fallen firmly in the group of ‘neglected diseases’—diseases in which pharmaceutical companies have been reluctant to invest due to a perception of low commercial potential. According to the World Health Organization (WHO), an estimated 1.7 million deaths resulted in 2004 from TB, and the global prevalence of TB was 14.6 million1. However, more than 80% of people with TB live in sub-Saharan Africa or Asia2, where spending on healthcare is low and access to drugs is limited. Owing to the low commercial interest in treating TB, no new drug class has been introduced for over 30 years. The current market is dominated by generic products. Relatively few international drug manufacturers market TB therapies; exceptions are Sanofi-Aventis, Pfizer and Sandoz (Novartis’s generics division). However, over the past 10–15 years, several factors have emerged, which are contributing to increased research and development (R&D) activity in TB treatment. The prevalence of TB grew significantly in the late 1980s and 1990s, driven by cases in sub-Saharan Africa, but also by a resurgence in both the US and Europe, where TB had been considered an eradicated disease. The WHO identified TB as a global health emergency in 1993 and launched the Global Plan to Stop TB, which focused on early TB diagnosis and reliable access to treatment. In areas of high HIV prevalence, coinfection with TB and HIV has become a critical issue, fuelling the increase in TB cases. Coinfection not only increases the proportion of individuals with TB who develop active disease, but also presents treatment challenges owing to interactions between TB and HIV drugs. Increased incidence of multidrug-resistant TB (MDR-TB) has further complicated effective disease management and created a demand for new treatments that are effective against resistant disease strains. The Global TB Alliance, a nonprofit organization working with public and private sectors to accelerate R&D in TB, was established in 2000. The TB Alliance has raised substantial funding for clinical research and is now the leading developer of new TB drugs, with agents in all phases of development. Nonprofit investment has been a key factor in stimulating interest in TB R&D within the pharmaceutical industry. Most products in the TB pipeline are joint projects between private and nonprofit organizations. The TB Alliance received donations of $39 million and $14 million from the Dutch and Irish governments, respectively3,4. In addition, the Bill & Melinda Gates Foundation provided grants of $25 million in 2000 and a further $104 million in 2006 (ref. 5).