As resistant tuberculosis rises, GSK says trial backs novel antibiotic

With cases of drug-resistant tuberculosis on the rise again around the world, GSK has sparked hopes of a new treatment option after reporting phase 2a data with a novel antitubercular drug for the disease.

The study of GSK3036656 – an inhibitor of the bacterial enzyme leucyl t-RNA synthetase (LeuRS) – showed that 14 days’ treatment with a low once-daily dose showed it was able to kill Mycobacterium tuberculosis in patients with drug-susceptible pulmonary tuberculosis, with no serious adverse effects.

The results suggest that GSK3036656 could become a component of new, simpler treatment regimens for TB, and its novel mechanism of action raises the hope that it could be used to tackle resistant TB strains.

Last month, the World Health Organization (WHO) warned that cases of drug-resistant TB had risen for the first time in two decades, primarily a consequence of the impact of the coronavirus pandemic on healthcare delivery.

Cases of drug-resistant TB (DR-TB) rose 3% in 2021 over the previous year, the first increase since record-keeping started in 2004, according to the WHO report, which called for countries to move quickly to restore access to essential services to treat the disease, as well as greater investment in new vaccines and therapeutics.

An estimated 10.6 million people contracted TB in 2021 and 1.6 million people died, the second year in a row that showed an increase on those metrics. Before COVID-19, the incidence of TB had been falling around the world.

At the moment, around 85% of TB cases can be treated with a four- to six-month drug regimen that, while effective in eliminating the infection, can be hard to adhere to and also carries a significant side-effect burden.

The short course needed for GSK3036656 and its good tolerability are important characteristics for any new TB drug, said GSK in a statement. The company is now planning to advance the antibiotic into a phase 2b/c programme that will look at its role in multiple antitubercular drug regimens.

Developing new TB treatment regimens is complicated, as they involve a combination of more than three compounds, often from different organisations.

“The aim is to identify a GSK3036656-containing regimen with sufficient tolerability, efficacy, and short enough duration to progress to phase 3 with a high probability of success,” added GSK.

Earlier this year, GSK made a commitment to invest £1 billion ($1.2 billion) over the next decade to accelerate R&D on infectious diseases, including TB, that disproportionately impact lower-income countries.

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