Clinical trial results presented at the Union World Conference on Lung Health in Paris on Wednesday provided evidence to support the use of four new, improved regimens to treat multi-drug resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB). 

The endTB clinical trial found three new drug regimens that can deliver similar efficacy and safety to conventional treatments while reducing treatment time by up to two-thirds. It also found a fourth regimen that can be used as an alternative for people who cannot tolerate bedaquiline or linezolid, staples in current World Health Organization (WHO) -recommended regimens for MDR-TB.  

Great news for multidrug-resistant #TB treatment today!⁰⁰The results of the @endTB clinical trial have found three new drug regimens which have shown similar efficacy and safety to standard treatments while reducing treatment time by up to two-thirds. https://t.co/JnTKKZ4j3G

— Christos Christou (@DrChristou) November 16, 2023

The endTB consortium, made up of Médecins Sans Frontières (MSF), Partners In Health (PIH), and Interactive Research and Development (IRD), began this Phase III randomized controlled trial in 2017.

A diverse group of 754 patients from Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa were enrolled and included teenagers and people with comorbidities like substance-use disorders.

It evaluated five nine-month treatment regimens against the standard of care, with three of the drugs showing favourable outcomes in 85-90% of participants. 

“We stand on the cusp of a significant breakthrough in the battle against MDR, a disease that disproportionately affects impoverished populations around the globe,” said Professor Carole Mitnick, co-principal investigator of the study. 

“But the cost of some drugs remains a barrier. One example is delamanid which is still priced at 12-40 times higher than it should be according to an independently estimated cost to produce the drug,” said Mitnick, Professor of Global Health and Social Medicine at Harvard Medical School.  

MDR/RR-TB is caused by a TB bacterium that is resistant to rifampicin, one of the most powerful first-line antibiotics, and also sometimes resistance to isoniazid as well. Roughly half a million people fall sick with MDR/RR-TB each year, and many die from it. 

Although a range of MDR-TB regimens are now in use around the world, many people are still treated with conventional treatments that take up to 24 months, are ineffective (only 59% treatment success in 2018), and often cause terrible side effects, including acute psychosis and permanent deafness.

All-oral treatments

“For far too long, MDR-TB has loomed as a formidable threat with limited, poorly tolerated treatment options, but today, we unveil evidence for multiple innovative all-oral, shortened regimens that will allow patient-centred, individualized treatment of MDR-TB,” said MSF’s Dr Lorenzo Guglielmetti, co-principal investigator.

“What makes these results even more remarkable is the diversity, and resulting generalizability, of this Phase III randomized controlled trial.”

The trial was funded by Unitaid, whose executive director, Dr Philippe Duneton, praised the “gold-standard research”.

“The drugs are already available where they are needed. If recommended, this high-quality evidence could quickly translate into better treatment options suitable for all people with drug-resistant tuberculosis.” 

Image Credits: The Global Fund / John Rae.