The World Health Organization (WHO) this week recommended three new regimens for multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) tuberculosis (TB) that are far shorter than the current regimens and can be taken orally.

The new regimens can cure patients in six to nine months rather than the usual 18 months and dispense with the painful injections that people with DR TB have had to endure as part of their treatment.

Almost half a million people contract MDR-TB/RR-TB every year, and many die from it – in part because it is hard for them to adhere to treatment.

“The use of new and repurposed medicines like bedaquiline, pretomanid, linezolid, and delamanid and the shift away from older injectable-based regimens has led to incremental improvements in the treatment success rate for people with MDR/RR-TB,” according to the WHO.

“Globally in 2022, in MDR/RR-TB patients who started treatment in 2021, the treatment success rate was 63%, reflecting a steady improvement from 50% in 2012 .”

Bedaquiline and delamanid are the first new TB drugs in 50 years.

Tested on wide range of patients

The WHO recommendations are based on results from the BEAT-TB clinical trial conducted in South Africa and the endTB trial conducted in seven countries between 2017 and 2023 by Médecins Sans Frontières’ (MSF), Partners In Health (PIH) and Interactive Research and Development (IRD), and funded by Unitaid.

Trial participants included children, adolescents, pregnant and breastfeeding women. 

“Clinicians can now offer these advances to nearly all patients, thereby increasing chances of cure while reducing exposure to treatment toxicity and reducing the spread of drug-resistant forms of TB in the community”, says Professor Carole Mitnick, PID Director of Research for the endTB project, co-Principal Investigator of the study, and Professor of Global Health and Social Medicine at Harvard Medical School. 

“With treatment complexity, duration, and toxicity reduced – and options increased – prospects for eliminating the gap between need (approximately 500,000 patients/year) and percentage treated (no more than 35%/year) are vastly improved,” she added.

Drug cost barrier

“WHO’s recommendations are a major step forward for the health of millions of patients affected by this form of the disease, which is particularly difficult to treat,” said Dr Lorenzo Guglielmetti, MSF’s director of the endTB project and co-principal investigator of the clinical trial.

“MSF carried out the endTB clinical trial – along with another TB trial called TB PRACTECAL – because the pharmaceutical industry failed to do so. Both trials have found better treatments for people with TB and influenced WHO recommendations and guidelines,” said MSF in a media statement released on Thursday.

“After several decades of therapeutic status quo – and for the second time in two years, along with TB PRACTECAL – new treatments evaluated by independent actors, including NGOs, have been rapidly incorporated by WHO into its recommendations for combating the scourge of MDR-TB,” added Guglielmetti. 

“It’s important to remember that the pharmaceutical industry, despite significant public financing, has only brought new drugs to market. They have not informed the use of these drugs in regimens. It has been left to NGOs to conduct controlled trials to inform practical use of, and innovations with, novel products.”

However, the success of the new guidelines rests on a reduction in the price of delamanid, which MSF described as “excessively high”. 

Japanese pharmaceutical corporation Otsuka produces delamanid through an exclusive licence with Viatris.

“We call on Otsuka and Viatris to stop blocking price-lowering generics from entering the market and to immediately share delamanid with every company interested in making more affordable quality-assured generic versions of this lifesaving TB drug,” said Christophe Perrin, TB advocacy pharmacist at MSF’s Access Campaign. 

“Otsuka and Viatris must also urgently drop their prices for delamanid so that many more people with DR-TB can access this lifesaving drug as part of shorter, all-oral regimens.”

Image Credits: TB Alliance.