TB Alliance applauds WHO’s rapid communication on key changes to treatment of drug-resistant Tuberculosis

New guidelines have potential to transform the TB treatment landscape with six-month standard

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New Delhi: TB Alliance, a global not-for-profit organization,  today applauded rapid communication regarding new guidelines for treating drug-resistant tuberculosis (DR-TB) released by the World Health Organization. For the first time, almost all patients with DR-TB can be treated in six months with an all-oral regimen.
Based on new clinical evidence presented and published over the past year, the new guidelines allow for the programmatic implementation of treating almost all forms of DR-TB with either BPaLM (a combination of bedaquiline, pretomanid, linezolid and moxifloxacin) or BPaL (bedaquiline, pretomanid and linezolid).
Dr. Mel Spigelman, President, and CEO TB Alliance, which developed pretomanid and first demonstrated the benefits of the BPaL regimen, said, “The WHO has just delivered excellent news for patients. This is a testament to what can be accomplished through long-term, sustained investments in TB research and development. We now have a path forward for handling the vast majority of cases of DR-TB with only six months of all oral treatment, with simplified drug regimens that have manageable side effects, and with cure rates on the same order of magnitude as the treatment for drug-sensitive TB.”
The rapid communication allows implementation of BPaLM and BPaL regimens under programmatic conditions, stating:
  • “The 6-month BPaLM regimen, comprising bedaquiline, pretomanid, linezolid (600 mg) and moxifloxacin, may be used programmatically in place of 9-month or longer (>18 months) regimens, in patients (aged ≥15 years) with MDR/RR-TB who have not had previous exposure to bedaquiline, pretomanid and linezolid (defined as >1 month exposure). This regimen may be used without moxifloxacin (BPaL) in the case of documented resistance to fluoroquinolones (in patients with pre-XDR-TB). Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged, but DST should not delay treatment initiation.”
The rapid communication also notes that:
  • “The data from the ZeNix study made it possible to identify the linezolid dose that offers the best balance in terms of efficacy and safety in patients aged above 14 years. The assessment of evidence from this study suggested that the optimal dosing of linezolid is 600 mg daily and that programmes should strive to maintain this dose throughout the treatment regimen to ensure optimal efficacy, with the possibility of dose reduction in the event of toxicity or poor tolerability.”
Pretomanid received its first regulatory approval in August 2019 for the treatment of people with certain forms of highly drug-resistant TB. BPaL was most recently evaluated in TB Alliance’s ZeNix trial, a Phase 3 clinical trial that took place in 11 sites across Georgia, Moldova, Russia, and South Africa. The BPaLM regimen was evaluated in the TB-PRACTECAL trial, sponsored by Médecins Sans Frontières/Doctors Without Borders (MSF), which compared three BPaL-based regimens to the local standard of care in the three countries where the trial was run (Belarus, South Africa and Uzbekistan). Primary safety and efficacy results for both ZeNix and TB PRACTECAL have been submitted to a peer-reviewed journal.
India has the world’s highest TB burden, with 2.6 million cases and close to 450,000 deaths each year. That’s more than 1 quarter of the global disease burden. India accounts for a quarter of the world’s DR-TB and fewer than 50% of patients put on treatment are having successful treatment outcomes.
India’s Prime Minister Mr. Narendra Modi has set an ambitious goal of TB eradication in India by 2025, ahead of the 2030 target of the Sustainable Development Goals. Pretomanid is a ‘Made in India’ product used as part of a six-month treatment regimen with reported efficacy of 90% and has the potential to contribute to India’s ‘TB Elimination program by 2025.
In July 2020, the Drug Controller General of India (DCGI) had approved the TB drug pretomanid (developed specifically for certain drug-resistant forms of the disease) for conditional access under the National Tuberculosis Elimination Program (NTEP), making India the second country in the world to provide regulatory approval for this product.
Ukraine was the first country to conduct operational research on how the BPaL regimen performed in clinical practice settings. Its reported preliminary findings also were consistent with the Nix-TB and ZeNix trials, but further implementation of the treatment was disrupted by the current invasion. The regimen has now been procured by more than 35 countries around the world. The number of people potentially eligible for treatment with either BPaLM or BPaL is approximately 500,000 each year.
The new guidelines could have significant implications on the decision-making of many high-TB-burden countries who are implementing efforts to control drug-resistant TB.