Prior to the onset of the Covid-19 pandemic, TB was the top infectious disease killer globally, with 1.4 million deaths per year and 10 million new infections. Despite the urgent public health need for new TB vaccines, there has been limited investment in vaccine development by manufacturers because of the unclear value proposition, and uncertainties in demand, procurement and return on investment for a vaccine that is almost exclusively targeted to low- and middle-income countries (LMICs). This uncertainty is amplified for TB vaccines intended for adults and adolescents, which are a new class of TB vaccines, where there is currently little incentive for industry to invest. This poses major constraints for progressing TB vaccine development.
The pipeline of new TB vaccines has never been as advanced as now, with 14 vaccine candidates in clinical trials: two in Phase I, eight in Phase II and four in Phase III (Table 1), including candidates to prevent TB infection and/or TB disease, and candidates to improve the outcomes of treatment. Of note, one of the candidates for use in adults and adolescents, M72, has demonstrated prevention of disease in adults, and is preparing to move into Phase III (Tait et al, 2019). In addition, results from the first Phase IIb TB vaccine clinical trial using a prevention of infection trial design indicated that BCG revaccination may protect high-risk, uninfected populations from TB infection (Nemes et al, 2018).
The engagement of vaccine manufacturers is crucial to produce clinical trial material for use in the pivotal license studies and to achieve licensure. However, ‘late-stage’ vaccine development (i.e. transitioning to phase III and beyond) is extremely costly, with high commercial risk and opportunity costs. For this reason, many vaccine candidates encounter the ‘second valley of death’ and do not proceed beyond clinical proof-of-concept. To mitigate this, there is a need to 1) fully chart the pathway through late stage product development, licensure and uptake in LMICs, 2) describe what activities are needed to navigate the complex process to country introduction while incentivizing and sustaining investment and 3) identify the stakeholders involved across the various stages.
The final agenda will be shared in due course.
