Tuberculosis remains one of the biggest threats to global health today. Despite efforts to control the disease in recent decades, it claimed over 1.6 million lives in 2021, with over 10.6 million people falling ill.
This is in part due to a lack of effective tools to fight the disease, such as tests and vaccines, and is an example of a global system of research and development that fails to meet demand.
Now, a late-phase clinical trial funded by Wellcome and the Bill & Melinda Gates Foundation seeks to advance a candidate vaccine – M72/AS01E (M72) – in communities most affected, with the potential to become the world’s first new tuberculosis vaccine in over a century if effective.
The urgent need for a new tuberculosis vaccine
Despite the need for innovation, progress to develop better prevention, diagnosis and treatment options for tuberculosis has been slow.
Vaccine development has been particularly stagnant, with only one approved in over a century: the Bacille Calmette-Guérin (BCG) vaccine. And while it has helped save many lives, the BCG vaccine has its limitations and offers very little protection against pulmonary tuberculosis (TB of the lungs) for adolescents and adults – which accounts for most cases and transmission.
While there have been some advances, including safer, shorter and more effective drug regimens, a lack of political will and financial investment remains a barrier to innovation.
Moreover, access to treatment is still a major challenge in low- and middle-income countries – which account for 80% of cases – for a number of reasons, including production monopolies, restrictive licensing terms and high prices.
This, combined with the impact of the Covid-19 pandemic and the rise of multidrug-resistant tuberculosis, has made the need for new and improved tools to protect against the disease more urgent than ever.
Funding the next generation of tuberculosis vaccine
Wellcome and the Bill & Melinda Gates Foundation have partnered to advance tuberculosis vaccine innovation while shifting the focus of research toward affected communities.
Together, they will fund a Phase 3 clinical trial testing the safety and efficacy of the M72 vaccine in countries with high rates of tuberculosis in Africa and South East Asia, sponsored by the Bill & Melinda Gates Medical Research Institute (GMRI).
To support the trial, which will cost an estimated US$550 million, Wellcome is providing up to US$150 million and the Bill & Melinda Gates Foundation will fund the remainder, about US$400 million.
People with and without latent tuberculosis will be included in the trial, as well as those living with HIV, for whom tuberculosis is a leading cause of death.
Initially developed by GSK, M72 has demonstrated its potential to reduce the risk of active tuberculosis in adolescents and adults in early clinical trials, including in people living with HIV.
Affected communities will be at the centre of the project, and partners will work closely with community advisory boards, local regulators and the World Health Organization to align on the trial design and ensure equitable and efficient access to the vaccine where it’s needed.
If proven safe and effective in the Phase 3 trial, M72 could become the world's first vaccine to protect adolescents and adults from pulmonary tuberculosis, the impact of which would be life-changing for communities burdened by the disease.
Transforming research and development for infectious diseases
Our mission at Wellcome is to reduce the risk and impact of infectious diseases globally by targeting the factors that contribute to their spread, including the systems that allow diseases to get out of control.
Progress against tuberculosis has remained slow and stagnant for decades due to limited scientific breakthroughs and a lack of equitable access to newer innovations. We want to advance innovation to protect global health – with a focus on accessibility and affordability.
But our involvement in the M72 trial extends beyond establishing the efficacy of a new vaccine. Rather, it builds upon our goal to reform the ecosystem of research and development for all infectious diseases.
One of our first steps toward this has been to develop a discussion paper outlining the problems that exist with the current system and potential solutions for change, which launched earlier in 2023.
This also extends to other areas of our funded work, including research to address barriers to vaccine development and help strengthen regulatory systems in African countries.
Building on this, and through new funding for tuberculosis, we seek to enhance the way clinical trials are conducted across the world and promote a more equitable regulatory environment. By working across government, industry and civil society, we aim to identify systemic changes that prioritise affordability, sustainability and equity at every stage of the process.
Through these efforts, we hope to help create new systems that support the development of affordable products and tools to fight tuberculosis and other diseases around the world.
Toward a reformed ecosystem for infectious disease
The ecosystem for infectious disease research and development does not support everyone that depends on it. We want to change that.
We've developed a discussion paper outlining some of the challenges and potential solutions for change.
We’re inviting those working across the ecosystem – including funders, policymakers, governments, regulators, industry and research organisations, civil society and affected communities – to read and provide feedback on this paper and its key topics.
There are two ways you can provide feedback:
What’s next for the M72 vaccine?
Due to begin in 2024, the Phase 3 trial will enrol approximately 26,000 people at more than 50 trial sites in Africa and South East Asia.
If found to be effective, M72 could be a transformative tool in the global fight against tuberculosis. But, its success alone cannot eradicate the disease.
Countries will need to use it alongside new and existing strategies, including effective diagnostics and drug regimens, to reduce the burden of tuberculosis. And in the meantime, access to other newer tools must be scaled up in line with World Health Organization guidance, including shorter and more effective treatment regimens, including preventative regimens.
Long-term solutions for tuberculosis require political commitment, sustained global partnerships, and continued investment in tuberculosis research and innovation. This includes expanding the pipeline of effective drug regimens, improving diagnostics and developing next-generation vaccines.
While new funding is a step in the right direction, the road ahead is long. Achieving meaningful change needs global and equitable collaboration.