Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, and with the rise of drug-resistant strains, treatment has become even more challenging. However, a significant breakthrough in the fight against drug-resistant TB has emerged from a global clinical trial led by Harvard Medical School, in collaboration with the endTB project. The findings, published on January 29 in The New England Journal of Medicine, reveal three new drug regimens that are both safe and effective for treating rifampin-resistant TB.

The endTB project, which includes partnerships with Médecins Sans Frontières, Partners In Health, Interactive Research and Development, and academic institutions worldwide, has made a major stride in improving treatment options for TB patients, particularly those resistant to rifampin, a key first-line antibiotic.

The newly developed regimens incorporate recently discovered drugs, offering doctors the ability to tailor treatments more effectively, reduce side effects, and replace painful daily injections with oral medications. This approach provides crucial alternatives for patients who are intolerant to certain drugs, face medication shortages, or struggle with growing antibiotic resistance.

The endTB trial is part of a broader global effort to test shorter, less toxic, and injection-free regimens for drug-resistant TB. The study tested five new, all-oral nine-month regimens using two groundbreaking TB medications—bedaquiline and delamanid—which were the first new drugs developed for TB in nearly 50 years. These two drugs were combined with older medications to find more effective, shorter regimens. A third drug, pretomanid, received emergency FDA authorization for use in 2019 but was not included in this study’s regimens.

The trial found that three new regimens were effective for 85 to 90 percent of patients, compared to 81 percent success with the control group, which received the standard of care, including longer treatments. These results indicate that the new regimens are not only effective but also offer an alternative that is less taxing on patients.

The endTB trial, which began in 2017, enrolled 754 patients across seven countries—Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa. The study aimed to improve the treatment for individuals with rifampin-resistant TB, a strain that affects an estimated 410,000 people globally each year. The WHO reports that only 40 percent of those with rifampin-resistant TB are diagnosed and treated, with a 65 percent success rate among those who receive treatment.

In another breakthrough, the endTB trial included previously overlooked groups, such as pregnant women, children, and those infected with HIV or hepatitis C. These groups are often excluded from clinical trials but were included in this research, marking a step forward in making TB treatments more inclusive. In August 2024, the WHO added the three new regimens from the endTB trial to its list of recommended treatment options for rifampin-resistant and multidrug-resistant TB (MDR-TB), with special provisions for pregnant women and other high-risk groups.

A key development in this trial is the increased affordability of treatment. Due to recent efforts to end patent exclusivity on bedaquiline, the cost of the newly recommended regimens has dropped to under $500—a target set by activists more than 10 years ago. This dramatic reduction in cost means that these new regimens will be accessible to more people than ever before, addressing one of the most significant barriers to treatment.

The endTB trial represents a new era in TB treatment, said Carole Mitnick, co-principal investigator of the trial and a professor at Harvard Medical School. “This Harvard-led partnership among NGOs, ministries of health, and academic partners has identified three new regimens that will make lifesaving care dramatically more accessible,” Mitnick explained. “We also resolved a critical question about how to use bedaquiline and delamanid to shorten and simplify treatment while retaining efficacy.”

Until recently, treatment options for TB were limited, often involving long, grueling regimens with daily injections and toxic medications that caused severe side effects. With the new regimens, the endTB trial offers renewed hope for millions of people suffering from drug-resistant tuberculosis worldwide, making treatment more effective, accessible, and sustainable.

By Impact Lab