Multidrug-resistant tuberculosis, the Médecins Sans Frontières study on a shorter and safer treatment, 89% effective

ROME – A new six-month regimen for the oral treatment of multidrug-resistant tuberculosis (MDR-TB) is safer and more effective than other existing regimens. This is confirmed by the results of a study by Doctors Without Borders (MSF) published a few days ago on New England Journal of Medicine. The results are from TB-Practecal, the first international randomized controlled trial evaluating the safety and efficacy of a six-month oral therapy recommended in the updated guidelines on treatment for tuberculosis (TB) of the United States. World Health Organization (WHO). It is the first time that the results of the TB-Practecal study have been published in a peer-reviewed medical journal.

A void has been filled. “It is a great satisfaction that the results of the study have been published in the New England Journal of Medicine after a rigorous peer-review process,” says Bern-Thomas Nyang’wa, MSF medical director and principal investigator on the study. “This publication will provide more in-depth data on who decides to use the TB-Practecal regimen in addition to the WHO recommendations. Until a few years ago, no new treatments for tuberculosis had been found in 50 years. This is because the disease does not directly affect the contexts where there are resources to fight it. With this study, MSF has tried to fill this gap. It is now essential that the new treatment is made available to all who need it.”

Enrolled 552 patients in seven countries. Trial enrollment, which ended in March 2021, included 552 patients at seven different sites in Belarus, South Africa and Uzbekistan. Currently, five MSF-supported countries have started implementing the brief treatment regimen with nearly 400 patients having started the treatment and eight more countries set to implement it in 2023. Launched in 2017, the TB-Practecal has tested three combinations of new treatments comparing them to locally accepted standard therapy, with positive results. A six-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) has been shown to be the most effective and safest. The study also examined a bedaquiline, pretomanid, and linezolid (BPaL) regimen and a bedaquiline, pretomanid, linezolid, and clofazimine (BPaLC) regimen.

The new BPaLM regimen is 89% effective. “We started the TB-Practecal clinical study nine years ago because something needed to be done. Patients told us that previous regimens were long, ineffective, grueling, and that the side effects were worse than the disease itself. Furthermore, the effectiveness was very low: only one in two people were cured. The new BPaLM regimen is 89% effective, is safer, shorter, better tolerated, and requires fewer medications,” says Dr. MSF’s Nyang’wa. MSF’s phase II/III clinical study found the new short-term treatment regimen BPaLM to be highly effective against rifampin-resistant TB and safer than standard therapy. 89% of patients in the BPaLM group were cured compared to 52% in the group treated with standard therapy, and fewer side effects were recorded in the BPaLM group than in the other group. The BPaLC and BPaL regimens also had better results than standard therapy.

The cost of therapy. While this new scheme gives hope to the 500,000 people who fall ill with DR-TB each year, currently the lowest global price provided to the Global Drug Facility (GDF) is around US$600 for a six-month course of BPaLM treatment, still above MSF’s maximum price of US$500. Bedaquiline, one of the other new TB drugs being developed by Johnson & Johnson with significant government and philanthropic support, has the lowest price at $270 for a six-month treatment, despite researchers estimating the drug could be manufactured and sold for less than $102 for a six month cure. In fact, all three regimens of TB-Practecal are likely to reduce treatment costs compared to the current standard of care.

MSF and TB. MSF is one of the largest non-governmental providers of TB care in the world. In 2021, 17,221 people followed by MSF started treatment for TB, including 2,309 people with DR-TB. MSF is working closely with national TB programmes, ministries of health and other key stakeholders to ensure this new regimen is available to people living with DR-TB as soon as possible.

TB-Practecal. The TB-Practecal is a multistage, controlled, randomized study with four arms. In phase 1, patients are enrolled in 4 different arms: 3 of these include experimental therapeutic regimens (BPaLM, BPaLC and BPaL) and one the standard control therapy. Phase 2 includes two arms: the experimental treatment arm (BPaLM) and the standard therapy arm.