TB Alliance: New TB Drug Approved to Treat the Deadliest Forms of TB

Product: Pretomanid

Product type: Drug

Disease: Drug-Resistant Tuberculosis

Tuberculosis (TB) is the leading infectious disease cause of death worldwide. In 2021, 10 million people fell ill from active TB and 1.6 million died.2[i] There is growing resistance to available drugs, which means the disease is becoming more deadly and difficult to treat. Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are difficult to cure and have high mortality rates even with treatment. Therapies for drug-resistant TB (DR-TB) have long required people to take drugs for 18 months or longer, and the World Health Organization (WHO) reports a global XDR-TB treatment success rate of 39 percent.[ii] There are close to half a million cases of drug-resistant TB annually, with XDR-TB comprising about 6% of those cases.[iii] More than 130 countries have reported cases of XDR-TB.[iv]

In August 2019, the U.S. FDA approved pretomanid for use as part of the “BPaL regimen” for the treatment of highly drug-resistant forms of TB, including XDR-TB. Pretomanid has subsequently been authorized by the European Commission, and approved by the Drug Controller General of India. In 2022, the World Health Organization guidelines for treating drug-resistant TB included a new recommendation on the use of a novel all-oral 6-month regimen composed of bedaquiline, pretomanid, linezolid and moxifloxacin.[v]

Pretomanid is the second drug approved for drug-resistant TB by the U.S. FDA in more than 40 years, and the first approved as part of a full treatment regimen. It is the first to be developed and registered by a not-for-profit organization. Prior to BPaL, XDR-TB patients were traditionally treated with combinations of up to eight antibiotics, including daily injections for 18 months or longer, with poor success rates. BPaL is approved as a three-drug, 6-month, all-oral regimen for people with highly resistant forms of TB. In clinical trial settings, it cured 90% of patients, which is comparable to outcomes with optimal therapy in drug-sensitive TB.[vi, vii] To date, more than 7,000 courses of BPaL have been ordered across more than 50 countries.

“With this breakthrough, the treatment of what we now call drug-resistant TB should be no more complicated, costly, lengthy or less safe or effective than that which is now available for what is presently termed drug-sensitive TB.”

—DR. MEL SPIGELMAN, PRESIDENT & CEO, TB ALLIANCE

BPaL generally reduces the cost per successful treatment by 65–80%. Research found that widely implementing the BPaLM/BPaL regimen to treat drug-resistant TB could save governments up to US$740 million annually, enough monies to fund almost another year’s worth of DR-TB treatments for more than 400,000 people.[vii]

TB Alliance initially in-licensed pretomanid in 2002, leading it through a full clinical development program; the FDA submission ultimately detailed data from a total of 19 clinical trials. Throughout its development, TB Alliance has collaborated with and received significant support from numerous governments, academia, philanthropic institutions, the private sector, civil society organizations, and other partners. This network of partners is representative of the unique PDP capabilities to build diverse and effective coalitions to drive global health innovation.

Coordination with private and public sector partners has continued since United States approval through global commercialization partnerships with Mylan, Macleods, Lupin, and Hongqi pharmaceuticals to advance regulatory applications around the world. Pretomanid was also added to the catalog of medicines of Stop TB Partnership’s Global Drug Facility, making it available to more than 130 countries, representing the vast majority of the global TB burden. These efforts ensured pretomanid was available around the world as quickly as possible after approval and that generic competition was in place immediately to help drive affordability and a stable supply. In 2022, Viatris, a global healthcare company, MedAccess, and TB Alliance have announced a new agreement to reduce the price of pretomanid by 34%.

With pretomanid, TB Alliance pioneered the concept of regimen development for TB—instead of developing a single drug to be added to existing treatments, pretomanid was developed only as part of a specific set of drugs comprising a fixed regimen. This approach can markedly accelerate clinical development, protect new drugs from developing resistance, and ensure that there is rigorous clinical evidence for the use of a specific combination. The regimen development model has since become the gold standard for TB research and is applicable to developing new therapies for other diseases that require treatment with multiple agents. The work related to regimen development has helped push the evolution of regulatory science to approve regimen-based clinical trials and accurately interpret their results.

TB Alliance’s 6-month, all oral DR-TB therapy reduces the length and number

of pills compared to the previous standard of care.

Photo by: Michele Spatari/AFP

i. Global tuberculosis report 2022. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO

ii. Global tuberculosis report 2020. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO

iii. Global tuberculosis report 2020. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO

iv. Global tuberculosis report 2020. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO

v. WHO operational handbook on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.

vi. Conradie F, Diacon AH, Ngubane, N. et al. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. New England Journal of Medicine. 382:893-902, March 5, 2020.

vii. Conradie F, Bagdasaryan T, Borisov S. et al. Bedaquiline–Pretomanid–Linezolid Regimens for Drug-Resistant Tuberculosis. New England Journal of Medicine. 387:810-823, September 1, 20222.

vii. Gupta A, Juneja S, Sahu S, Yassin M, Brigden G, Wandwalo E, et al. (2022) Lifesaving, cost-saving: Innovative simplified regimens for drug-resistant tuberculosis. PLOS Glob Public Health 2(11): e0001287. https://doi.org/10.1371/journal.pgph.0001287