The first new tuberculosis vaccine in 100 years may be within reach, after the announcement that more than $500m (£395m) has been pledged by philanthropic institutions for final trials involving 26,000 people in Africa and south-east Asia.
The M72/AS01E vaccine, developed by the giant pharmaceutical company GlaxoSmithKline, was shown to be 50% effective in phase 2b trials in 2018, but the company pulled out rather than invest in the large-scale trials needed for a licence, saying it did not see a market.
In 2020, GSK passed the licence to the Bill & Melinda Gates Medical Research Institute, a biotech nonprofit spin-off from the Bill & Melinda Gates Foundation. The foundation, which was already investing in the vaccine, will put up around $400m for the phase 3 trials, while the global charitable organisation Wellcome will provide up to $150m.
“TB remains one of the world’s deadliest infectious diseases,” said Julia Gillard, the chair of Wellcome. “The development of an affordable, accessible vaccine for adults and adolescents would be gamechanging in turning the tide against TB.”
Vaccines for Covid were developed from scratch in less than a year, yet there have been no new vaccines for TB, which kills 1.6 million people a year, since the BCG (Baccilus Calmette-Guérin) was introduced in 1921. All UK schoolchildren were once vaccinated with the BCG, but it is now recognised as effective only in the very young, and lasts only a few years.
Up to a quarter of the world’s population is infected with the TB bacteria, which can remain latent but be passed to other people, or cause active disease. TB predominantly affects impoverished populations in Africa and Asia, although there are serious problems in eastern Europe and cases of multi-drug resistant TB across the globe.
Bill Gates, the co-chair of the Gates Foundation, said: “With TB cases and deaths on the rise, the need for new tools has never been more urgent. Greater investment in safe and effective TB vaccines, alongside a suite of new diagnostics and treatments, could transform TB care for millions of people, saving lives and lowering the burden of this devastating and costly disease.”
The five-year hiatus between the exciting 2018 results in 3,000 people with latent TB and Wednesday’s announcement was spent in negotiating the licence handover and transfer of manufacturing from GSK to Gates, and in investigating the best 50 sites in TB-endemic regions for the final trials.
“When the results were really strong, there was a tremendous interest in the global health community in moving forward to phase 3,” said Trevor Mundel, the president of global health at the Gates Foundation. “GSK at that point indicated that this was not going to be a commercial vaccine for them. We negotiated a licence with GSK, which was executed in 2020.
“Then we had the discussions and negotiations with the Wellcome Trust around co-funding the project because it was an enormous enterprise for both our organisations.”
Governments need to come onboard such large projects, which are of crucial importance to health worldwide, say the organisations. “We hope that M72 is going to be the first of a number of progressive TB vaccines that will be extremely useful. And for that, I think we need this broader set of funders,” said Mundel.
“We would certainly look to governments, and as much as I’ve said that TB is a disease of poverty, it remains rife in many middle-income countries, even in richer regions of the world. Covid has given us all the sense that there are no national barriers that you can hide behind for a global transmission problem like TB. Not paying attention to it, even if you may have a low incidence in your own geography, opens you up to transmission, with increasing migration and the like,” he added.
The phase 3 trial will start early next year, and last between four and six years. Researchers will track the numbers of people with latent TB who convert to active TB. If the vaccine is as successful as it showed itself five years ago in a smaller number, it will prevent half the cases of active disease that would have been expected.
The World Health Organization says that a vaccine with 50% efficacy could prevent up to 76 million cases and 8.5 million deaths over 25 years. It would save billions in costs for families whose wage-earners are hit by the illness and often have to pay to travel for treatment.
The Treatment Action Group (TAG) welcomed the “historic” investment. “We hope this funding commitment sparks governments and other funders to substantially increase investments in the TB vaccine pipeline, which contains a number of promising candidates but faces a dire financial shortfall,” said the TAG executive director, Mark Harrington, who urged all involved to improve access to the vaccine should it be approved.