Finally, there is some good news for drug-resistant strains of tuberculosis (TB). A new therapy protocol has been developed that could work. Results of a ZeNix phase III clinical trial has found that the BPal treatment regimen remains effective against highly drug-resistant strains of tuberculosis with a reduced dosage. “This is going to be a game changer, especially for a high burden country like India,” says Dr Vikas Oswal, member of the national technical expert group, Central TB division, Government of India.
Why is this an eventful development in TB therapies?
Efforts have been going on to develop improved drug/s for TB, especially drug-resistant forms of the disease, which are more difficult to treat and entail the administration of highly toxic drugs. The Global TB Report 2021 stated that the mortality rate due to all forms of TB between 2019 and 2020 increased by 11 per cent in India. In absolute numbers, the total number of estimated deaths from all forms of TB, excluding HIV, for 2020 was 4.93 lakh (4.53-5.36 lakhs) in the country, 13 per cent higher than the 2019 estimate. It’s useful to remember that India is also one of the top high-burden countries for MDR/RR-TB as estimated by the WHO for 2021–2025. It is against this backdrop that the recent development assumes significance.
What are the trial results?
The results from the trial, which was led by the TB alliance, a non-profit TB drug developer, were published in the New England Journal of Medicine on Thursday. ZeNix is a clinical trial testing the BPal regimen, which consists of Pretomanid, Bedaquiline and Linezolid. The trial was commissioned to evaluate if the efficacy of the BPal drug regimen can be maintained while reducing its toxicity through a lower dose and shortening the duration of Linezolid. It took place across 11 sites in Georgia, Moldova, Russia and South Africa. Uniformly, they have shown that BPal treatment remains effective against highly drug-resistant TB strains. The success rate for trial participants receiving a variable dosage of linezolid (600-1200mg) as part of the BPal regimen was between 84 to 93 per cent. “These results add to the substantial evidence base for the efficacy and safety of the BPaL regimen and will enable care providers to further optimise use of the regimen,” said Mel Spigelman, M.D., President and CEO of TB Alliance.
Will we be testing the BPal regimen of drugs in India?
“The results have a promising outcome for India and at present an ICMR trial is under way across 13 sites in the country to test it,” says Dr Oswal, who is also the principal investigator of the trial site in Mumbai. “We have the highest number of drug-resistant TB in Mumbai – this regime is definitely a promising one and we are looking forward to it. The present treatment has 13-14 drugs daily given for a period of 18-24 months. The BPAL regimen has a maximum of three to four drugs daily where it can be given only for six months – The trial in India was kickstarted at Shatabdi hospital in October last year and we have enrolled patients across 13 sites in the country. The trial is under way but we are hoping to roll out the BPal regimen soon,” Dr Oswal said.
What is drug-resistant TB?
Drug-resistant TB develops when the long, complex, decades-old TB drug regimen is improperly administered, or when people contract TB from others who have drug-resistant disease—highlighting the urgent need to develop better and shorter treatment regimens. Only an estimated one third of people with drug-resistant TB infections received treatment in 2020.
BPaL: What it is, and why it’s important?
Developed by a non-profit organization, TB Alliance, Pretomanid is the newest anti-TB drug, prescribed as part of the BPaL regimen, which includes two other drugs – Bedaquiline and Linezolid. Medical practitioners are hoping that this new drug in the BPaL combination will drastically cut short the treatment duration by half (and more), and reduce the amount of medication an MDR-TB patient must take during treatment. From a treatment duration of 18 to 24 months, the BPaL is likely to bring down treatment time to around six months. Furthermore, the older “all oral drug regimen”, included nearly 14 different anti-TB drugs for a patient to take every day. With BPaL, it is likely to take just three daily tablets. A shorter regimen, which is all oral and requires lesser doses per day, makes it easier for a patient to adhere and complete treatment.
Why is there a need for shorter treatment regimens?
Currently, India has a 56 per cent treatment success rate for MDR/RR-TB cases, and 48 per cent for XDR-TB cases, attributable to long and toxic drug regimens. Active TB must be treated with a combination of drugs; the most drug-sensitive forms of TB require at least four months of treatment using four anti-TB drugs. An estimated 1.5 million people died of TB in 2020, according to the World Health Organization (WHO), although the precise numbers are not known and recent research suggests that TB could have killed many more people.