Multidrug-resistant TB (MDR-TB) remains a public health crisis. As per WHO's Global TB Report 2016, 480,000 people fell ill with MDR-TB in 2015, with 3 countries - India, China, and Russia - carrying the major burden and together accounting for nearly half of all MDR-TB cases globally.
Detection and treatment gaps continue to plague the MDR-TB response. In 2015, only 1 out of every 5 people needing treatment for MDR-TB were able to access it and only 52% of those who started MDR-TB treatment were cured.
"These sobering statistics remind us of our urgency to continue the fight to develop better, faster and affordable treatments that will finally bring this pandemic under control," said Dr Mel Spigelman, CEO of TB Alliance, which is working to advance several promising regimens to tackle all forms of TB.
The current MDR-TB regimen lasts for 2 years or more. It includes medicines and injectables that are not only toxic but also come at a cost that is higher than what many patients and healthcare systems can afford. Even the new 9 month MDR-TB regimen that has recently been endorsed by WHO, though shorter, does include 4 months of injectables.
However new results from 2 clinical studies conducted by TB Alliance point to an emerging paradigm, where countries may soon have the short, all-oral, and affordable drug regimens needed to treat all people with TB. Late stage clinical results from these two studies were unveiled yesterday at the 47th Union World Conference on Lung Health in Liverpool.
The NC-005 study
The NC-005 study investigates an oral, injection free regimen that purports to treat both drug-sensitive and MDR-TB with a short, simple, safe, and affordable treatment. A Phase 2b, 2 month study tested various combinations of BPaMZ--Bedaquiline (B), Pretomanid (Pa), Moxifloxacin (M) and Pyrazinamide (Z). It was conducted at 10 sites in 3 countries (Uganda, South Africa, and Tanzania). A total of 240 patients were enrolled in the study-- 180 patients with drug-sensitive TB received BPaZ and 60 patients with MDR-TB received BPaMZ. The study also investigated a simpler dosing scheme for bedaquiline, which could lead to fewer pills and an overall less complicated treatment for patients.
NC-005 showed that the best regimen was a combination of all four drugs, BPaMZ, which was examined in an arm of the trial. Data showed that at the end of 2 months, clinical study participants receiving BPaMZ cleared TB bacteria from their sputum 3 times as quickly as those on the standard treatment regimen. Almost all participants had culture conversion after the 2 months of treatment. This is the fastest rate of culture conversion that has ever been seen and indicates the potential of BPaMZ to treat all forms of TB-drug-sensitive as well as MDR-TB with the same regimen. The regimens appeared safe. The study showed that it was possible to simplify the dosing of Bedaquiline and found that a daily dose of Bedaquiline (200 mg) is at least as active and safe as the labelled dose. This will allow for simpler daily dosing with the regimen and to be combined in a fixed dose combination.