For decades, those living with tuberculosis (TB) and their providers have operated in conditions of scarcity and neglect: inadequate funding for programmes and research, aging infrastructure and outdated technologies, limited scientific understanding, knowledge gaps on existing treatments, low public attention, and absent political will.
According to a Pipeline Report, the limited response to TB born of these conditions remains entrenched, even with two new drugs conditionally approved by stringent regulatory authorities, and a new global strategy to end TB from the World Health Organisation (WHO) that envisions a world free of TB (with a 95% reduction in TB deaths and 90% reduction in TB incidence by 2035 compared with 2015 levels),3 and a relative increase in resources for TB drug development since 2006.4 (Though funding for TB research and development (R&D) is still grossly insufficient, investments in TB drug research, which amounted to $255m in 2013, have reached just one-third of the annual target set by the Global Plan to Stop TB, 2011–2015
To their credit, TB treatment researchers are making the most of what they have, cobbling together combinations and treatment strategies to better use existing medicines and the few new and experimental drugs available, as well as exploring adjunct, host-directed therapies to improve treatment. For the first time since 2009, a new drug candidate recently entered phase I. Studies are at last under way or coming together to test new drugs in smarter combinations to determine the safety of co-administration and optimal regimens for multidrug-resistant TB (MDR-TB). Innovative trial designs are attempting to shorten treatment for drug-sensitive TB (DS-TB), and improved preventive therapy for TB, including for MDR-TB, is progressing.
But for the most part, these research efforts won’t bear fruit for years. Drug sponsors are slow or unwilling to collaborate, pharmaceutical investment is minimal, and TB treatment trials remain lengthy. This work should have advanced long ago – but better late than never.
In the meantime, TB programmes, donors, multilateral agencies and non-governmental organisations providing technical assistance, and pharmaceutical companies have been halting and unambitious in rolling out available strategies and new technologies. Nearly half a million people develop MDR-TB a year, yet less than one in three is diagnosed, and only one in five starts treatment.
According to estimates based on WHO guidelines, bedaquiline or delamanid is clinically appropriate for a third of those who develop MDR-TB (160,000 people per year). Yet despite bedaquiline’s being approved for two-and-a-half years, fewer than 1,000 people worldwide have received it outside of a clinical trial. A bedaquiline donation programme that opened in April 2015 could improve access if implemented properly, though drug donations are by definition a limited and unsustainable approach. Access to delamanid has been far worse, with fewer than 200 patients receiving it outside of studies, even though it was approved over a year ago. TB drug research and programming alike need an infusion of urgency, coordination, and funding.
Preventing TB requires infection control to avert transmission and preventive therapy for subclinical TB infection (often referred to as latent TB infection, or LTBI, as it is asymptomatic and is not transmissible), as an improved vaccine is years away. Modelling demonstrates that rapidly reducing TB incidence and death on the path to elimination depends on treating both active TB disease and TB infection. With an estimated one-third of the world’s population infected with TB, we need a much better understanding of who is most at risk of progression from TB infection to active TB disease to target prevention efforts.Pipeline Report material