After 20 years of improvements, tuberculosis control and funding have nosedived in the wake of the COVID-19 pandemic.
Global investments in TB research and development totaled just $723 million in 2021, which Stop TB Partnership said is “far short” of the $2.16 billion needed annually, according to the 2022 G-Finder report from Policy Cures Research.
In addition, the report shows an “alarming decline” in product development partnerships between the pharma industry and academic research institutions for neglected and poverty-related diseases such as TB.
This is especially significant because TB must be treated with multiple drugs, making collaboration between pharma companies, nonprofits, governments and other organizations crucial to success.
“Some of the gains that were made in TB control for the past 20 years globally seem to have been reversed, so the number of TB cases estimated by the World Health Organization has increased to 10.6 million in 2021, the year we have the most recent estimates,” said David Holtzman, clinical development leader at Bill & Melinda Gates Medical Research Institute (Gates MRI), whose work focuses on TB drug development.
“And even more worrisome, probably, is the number of deaths due to TB increased in that year to 1.6 million,” Holtzman continued. “And that number had been steadily declining for quite a long time.”
Despite this ongoing — and now increasing — need, TB treatments haven’t changed much in about 40 years.
In the research arena, though, promising new drugs could alter that landscape. Here are a few updates from the world of TB treatment innovation:
Key drug development partnerships
Gates MRI and Calibr, a division of Scripps Research, have partnered to advance development of a new treatment for tuberculosis called CLB-073. Gates MRI will have the exclusive license to continue development of the investigational compound.
“This is a compound that has shown some great promise in the preclinical space for treating TB and for shortening TB treatment,” Holtzman said. “We're excited about it because it has a novel mechanism of action, targeting the cholesterol metabolism that TB uses — TB actually uses cholesterol as an energy source, so this compound interferes with that.”
Late last year, Gates MRI also entered into a licensing agreement with Merck & Co. to evaluate two preclinical antibacterial candidates as potential components of combination regimens for TB treatment. One of them was MK-7762, for which Gates MRI launched a phase 1 trial in healthy volunteers in February, Holtzman said.
A study by the nonprofit TB Alliance showed that a new combo drug regimen produced high efficacy and could shorten treatment for TB in drug-susceptible or drug-resistant TB patients. The late-stage clinical trial evaluated the BPaMZ regimen, consisting of bedaquiline, pretomanid, moxifloxacin and pyrazinamide. However, the study also revealed adherence challenges, with approximately 10% of patients on the BPaMZ regimen discontinuing treatment due to side effects.
"Some of the gains that were made in TB control for the past 20 years globally seem to have been reversed."
David Holtzman
Clinical development leader, Gates MRI
TB Alliance also entered into a license agreement with South Korean biotech Qurient to develop and commercialize telacebec (Q203), a first-in-class cytochrome bc1 inhibitor pill for the treatment of TB and other non-tuberculosis mycobacterium infections.
Meanwhile, the Korean nonprofit research institute Institut Pasteur Korea reported that it has developed new lead compounds for drug-resistant TB with the AI drug discovery and development company Standigm.
Shifting treatment guidelines
WHO updated and consolidated guidelines on the treatment of drug-resistant TB with a regimen that offers better outcomes and remarkably shortens the duration of treatment, the organization said. Included in the new recommendation is the use of an oral six-month regimen composed of bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM).
The CDC is also changing how these treatments can be monitored to better suit the widespread need and directly observed therapy (DOT) conducted via video for TB patients should be considered equivalent to in-person DOT, according to new agency guidelines.
DOT “involves observing a patient ingest medication, monitoring the patient for adverse events, and providing support for treatment completion,” the CDC said, and is considered the care standard for TB treatment.
Although patient observation has historically been done in person, the new guidelines say that doing it via video is not only just as effective, but can improve patient satisfaction, save time and money, and allow DOT where it might not have otherwise been feasible.
