Initial results from a phase 2/3 trial of an all-oral, 6-month treatment for drug-resistant tuberculosis (DR-TB) indicate that the regimen is significantly more effective than the standard regimen, researchers announced this week at an international conference.
The data from the TB-PRACTECAL trial, presented at this week's Union World Conference on Lung Health by researchers with Medecins Sans Frontieres (MSF), showed that 89% of rifampicin-resistant (RR)-TB patients treated with the 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) were cured, compared with 52% of patients who received the standard of care.
In addition, fewer patients who received the new regimen had major side effects (40% vs 80% with the standard regimen), and none died. Four patients in the standard-of-care group died from TB or treatment side effects, according to an MSF press release.
The trial was conducted in seven sites in Belarus, South Africa, and Uzbekistan and enrolled 552 patients, 301 of whom were included in the results. MSF said it plans to publish the data, which has not yet been peer-reviewed, later this year.
Shorter, less toxic regimen
The BPaLM regimen is a derivation of the BPaL regimen, which was approved for patients with extensively drug-resistant (XDR)-TB and treatment intolerant or non-responsive multidrug-resistant (MDR)-TB in 2019. The 6-month, all-oral treatment is significantly shorter and less toxic than the standard regimens for drug-resistant forms of the disease, which can last from 18 to 24 months and include painful injections.
Previous clinical trials—such as the Nix-TB and ZeNix trials—have shown the BPaL regimen to be highly effective, with a treatment success rate of 90% and higher. The overall treatment success rate reported in 2018 for people treated for MDR/RR-TB with standard second-line regimens was 59%, according to the World Health Organization (WHO). The length and the toxicity of the standard treatment are often cited as the primary reasons for its low success rate.
MSF, which is sponsoring the TB-PRACTECAL trial, says it's also planning to share the data with the WHO in hopes that it will inform the agency's upcoming review of DR-TB treatment guidelines and shape national treatment guidelines. Globally, the WHO estimates that roughly 465,000 people fall ill with DR-TB each year.
"When we embarked on this journey, patients with DR-TB around the world were facing lengthy, ineffective, and grueling treatment that disrupted their lives," Bern-Thomas Nyang'wa, MD, MSF medical director and chief investigator of the trial, said in the press release. "These results will give patients, their families, and health care workers worldwide hope for the future of DR-TB treatment."
In related news, researchers from Ukraine, which has the third-highest caseload of DR-TB in the world and is the first country to conduct operational research on how the BPaL regimen performs in clinical settings, presented preliminary data from their investigation at the same conference. Their data showed that among the first 55 patients recruited, 46 completed their 6-month treatment and were sputum negative at the time of assessment, according to a press release from the TB Alliance.
"The evidence we’ve seen from these studies—from Nix-TB to ZeNix, operational research, and now in TB-PRACTECAL—underscores the potential of short, all-oral BPaL-based regimens for patients," Mel Spigelman, president and CEO of TB Alliance, said in the release. "We look forward to advancing our work to find better cures for all forms of TB and exploring new pathways and therapeutic approaches to treat this deadly infectious disease."
According to TB Alliance, which developed pretomanid and has been among the groups pushing for shorter and more effective DR-TB treatments, more than 28 countries have procured the BPaL regimen or will soon be providing it to patients under operational research guidelines, which require patients to be monitored and tracked.