Toward Improved TB Treatment for All

Since the approval of pretomanid and the BPaL regimen, TB Alliance and partners have worked continuously to optimize the regimen to provide the best possible treatment experience and outcomes for the largest number of people. The evolution of BPaL has included a reduction in daily linezolid dose and the recommendation by the WHO to use BPaL with or without moxifloxacin in nearly all people with drug-resistant TB. In 2023, major steps were taken to further grow the populations who can benefit from pretomanid. These advances include the launch of a Pan-Phase 2 clinical trial (NC-009), testing pretomanid and linezolid in combination with a new compound, TBAJ-876, in people with drug-sensitive TB, as well as the first trial of pretomanid in participants under the age of 14. TB Alliance’s vision for TB research and development (R&D) prioritizes the pursuit of universal regimens—meaning that virtually all people with all forms of active TB can be treated with the same therapy. These new trials are significant steps toward optimizing pretomanid-based regimens as universal therapies.

Testing a “Universal Regimen”

Late in 2023, TB Alliance launched NC-009, a new Pan-Phase 2 clinical trial incorporating elements of Phase 2a, b and c trials. NC-009 aims to evaluate the safety and efficacy of a combination of a new experimental compound, TBAJ-876, with pretomanid and linezolid. Results from preclinical and Phase 1 studies showed that TBAJ-876, eliminated TB bacteria faster and had a potentially safer profile than bedaquiline (a drug of the same class). This regimen has the potential to shorten and improve treatment for both drug-sensitive and drug-resistant TB and may serve as a true universal regimen. If successful, such a breakthrough would allow virtually all people with TB to be treated with the same regimen, dramatically simplifying TB treatment.

Landmark Agreement to Advance Development of New TB Treatment

In early 2023, TB Alliance and Qurient Therapeutics, a biotechnology company based in South Korea, entered into a license agreement to develop and commercialize telacebec (Q203), a first-in-class cytochrome bc1 inhibitor for the treatment of TB and other non-tuberculosis mycobacterium (NTM) infections. Q203 has shown potential against drug-resistant forms of TB, as well as against Buruli ulcer, a chronic, necrotizing disease that affects a person’s skin and sometimes bone, and leprosy, a debilitating, disfiguring, and stigmatizing disease.

New Research to BENEFIT Kids

The BENEFIT Kids program, funded by UNITAID and led by Stellenbosch University in collaboration with TB Alliance, aims to address the lack of high-quality evidence on access to medicines to prevent and treat drug-resistant TB in children. Throughout 2023, BENEFIT Kids published a series of research papers in the International Journal of Tuberculosis and Lung Disease (IJTLD) highlighting the importance of child-friendly formulations for DR-TB, including community perspectives on child-friendly formulations and a novel home-based method for preparing suspensions. This at-home method was also demonstrated by Dr. Raj Taneja, Vice President, Pharmaceutical Product Development at TB Alliance, at the 2023 Union Conference in Paris.

Photo: Michele Spatari/AFP

SPOTLIGHT: Advancing Child-Friendly Medicines

TB Alliance has enrolled its first participants in a Phase 1 pediatric clinical trial evaluating the pharmacokinetics (PK), safety, tolerability, and acceptability of the TB medicine, pretomanid – an important step in making the BPaL/M regimens, recommended by the World Health Organization (WHO) for treating adults with drug-resistant TB, appropriate and available for children.

This trial is an important step in bringing life-saving technologies to our littlest patients.
— Pauline Howell, co-principal investigator, Sizwe Tropical Disease Hospital, Johannesburg
Annual Report 2023