GSK’s TB vaccine makes a big step forward towards licensing

GlaxoSmithKline has spent 20 years trying to develop an improved vaccine for tuberculosis, and new data for its lead candidate M72/AS01E suggests it is getting closer to a breakthrough in the disease.

A phase 2b trial has found that the vaccine has an overall protective efficacy of 50% three years after immunisation, an advance on the current BCG vaccine which is not very effective and according to GSK “does not provide proven and consistent protection in adults in TB-endemic countries.”

The big problem with the BCG shot is that its protection tends to be short-lived. That means it provides limited protection in people with latent TB infection – estimated to be around a quarter of the global population – who go on to develop active TB disease later on.

Meanwhile, the drugs used to treat TB are progressively becoming less effective due to the emergence of resistant strains, so there is an even more urgent need for an effective vaccine. Earlier this year, the WHO warned that multidrug resistant TB could become the dominant form of the infection in Europe as well as the rest of the world.

M72/AS01E still needs further testing and is likely a few years away from being licensed, but the new data adds to optimism that improved protection may in time be available for a disease that kills around 1.5 million people around the world every year.

The three-year data – published in the New England Journal of Medicine and presented at the World Conference on Lung Health this week – builds on an earlier readout from the trial in 2018, which found a 54% success rate after two years.

TB expert David Lewinsohn of Oregon Health & Science University in the US told the BBC that the remarkable finding in the trial is that M72/AS01E is effective in adults who are already infected with Mycobacterium tuberculosis, the bacteria that causes TB.

“As most people who are infected with Mycobacterium tuberculosis do not get TB, we believe that infection confers some degree of protection,” he said. “As a result it is really exciting that a vaccine has been shown to improve on this natural immunity.”  

The trial was conducted in three countries where TB is endemic – Kenya, South Africa and Zambia – and involved 3,573 HIV-negative adults between the ages of 18 and 50 years who received two doses of either M72/AS01E or placebo 30 days apart.

The subjects were followed for three years to see if they developed pulmonary TB disease, the most contagious form. In the final analysis, 13 participants in the vaccine group developed active pulmonary TB compared to 26 participants in the placebo group.

“Without a more effective vaccine, it will not be possible to achieve the WHO target of decreasing the number of new cases by 90% and the number of TB deaths by 95% between 2015 and 2035,” said GSK in a statement.