Grania Brigden, TB advisor to the MSF Campaign for Access to Essential Medicines, describes how the current drug R&D model is failing TB patients.
At last week’s Union World Conference on Lung Health, TB patients finally took centre stage, with patients invited to describe the realities of the 2-year treatment regimen for MDR-TB and advocacy groups storming events to call for greater vision in TB treatment and research. Their stories and concerns mirrored those shared with Médecins Sans Frontières (MSF) in a manifesto for better treatment for drug-resistant TB and in blogs by MDR-TB patients.
Patients are right to be concerned. In the past year, there has been no improvement in WHO estimates for MDR-TB: fewer than a third of patients were detected; 170,000 people died; 17,000 patients were diagnosed but not started on treatment; and only 48% of those started on treatment were cured.
So why are so few patients receiving treatment? With treatment costing approximately $4000 per patient lack of funds is a major factor. Another is lack of capacity to scale up treatment programmes to match demand. But even when the funding and political will are there, the current treatment regimen is so problematic that scaling up is a struggle. A review of an MSF project in Uzbekistan published this week in PLOS ONE highlighted the challenges: when the MDR-TB programme was scaled up, default rates rose above 20%.
Patients are demanding shorter, more effective and less toxic treatment regimens. These demands will not be met without urgent investment in R&D. The importance of R&D was recognised at the Union Conference, with this year’s STOP TB Symposium highlighting the need for new innovations in all aspects of TB care. And WHO has acknowledged the importance of R&D by making it a key aspect of the post-2015 global TB strategy. But despite this welcome interest, the current R&D model for TB drug development is not fit for purpose. The drug pipeline is weak with no drugs in phase I trials, and underinvestment is chronic and falling by $30.4 million, leaving a shortfall of $1.39 billion.
The worst indictment against the current framework is that although there are finally two new classes of TB drugs on the near horizon (bedaquiline and delamanid) we lack the evidence on how to combine them in a game-changing regimen. There are a number of groups looking at developing new regimens, but progress has in part been hampered by an R&D framework that lacks collaboration as well as a lack of political will and investment. In an article published early online this week, MSF and partners outline principles that could be used to design a shorter, better-tolerated MDR-TB regimen that meets the needs of patients and clinicians.
After all for TB, drug regimens are needed rather than just single drugs. We need to move away from the current model that encourages the development of single drugs in isolation. A new framework is needed that encourages open, collaborative research, has sufficient incentives to pull drugs from pre-clinical to clinical development and can accelerate new combinations for regimens at a much earlier stage. And the framework must consider the needs of patients and the realities of delivering treatment in the settings where MDR-TB is most prevalent. It is time for researchers, drug manufacturers, national TB programme leaders and international health organisations to show that they have the vision and ambition to meet the demands of TB patients around the world.