Phase 2 Trial Shows TB Treatment Could Be Shorter

Sorfequiline, formerly referred to as TBAJ-876, was tested alongside pretomanid and linezolid in a randomized, controlled study involving in...

Sorfequiline, formerly referred to as TBAJ-876, was tested alongside pretomanid and linezolid in a randomized, controlled study involving individuals with drug-sensitive tuberculosis.

COPENHAGEN (November 19, 2025)—Recent clinical trial findings shared by TB Alliance at the Union World Conference on Lung Health indicate that the new antibiotic drug sorfequiline (TBAJ-876), a next-generation diarylquinoline, could enhance tuberculosis (TB) treatment when used alongside pretomanid and linezolid in a regimen called "SPaL."

The NC-009 trial(A pan-Phase 2 clinical trial) found that, in general, sorfequiline was more effective than bedaquiline. The 100 mg SPaL regimen demonstrated better effectiveness against TB compared to the standard HRZE treatment (isoniazid, rifampin, pyrazinamide, and ethambutol), suggesting the possibility of reducing the duration of treatment for active TB. Moreover, the SPaL regimen showed a similar safety record to the standard treatment for individuals with drug-sensitive TB (DS-TB).

The TB Alliance carried out the study across 22 locations in South Africa, the Philippines, Georgia, the United Republic of Tanzania, and Uganda.

Science keeps advancing, benefiting healthcare systems, people with TB, their families, and their communities," stated Dr. Mel Spigelman, President and CEO of TB Alliance. "The creation of the BPaL regimen enabled us to cut the treatment duration for most drug-resistant TB to six months, a significant breakthrough for patients. Now, we have a chance to make treatment even shorter — marking an important step toward our objective of creating an ultra-short regimen that can address both drug-sensitive and drug-resistant TB.

Both sorfequiline and bedaquiline are part of the diarylquinoline family of antibiotics, which attack a crucial enzyme in tuberculosis bacteria responsible for energy generation. In 2012, bedaquiline received approval for treating drug-resistant TB, marking it as the first new antibiotic to be authorized in many years. Nevertheless, in recent times, there has been an increase in TB strains that show resistance to bedaquiline.

The TB Alliance has been working on sorfequiline throughout the entire research and development process, starting from initial discovery to its current stage of advanced clinical trials. Study results indicate that sorfequiline may offer a more favorable safety profile compared to bedaquiline, as well as the ability to target various strains that are resistant to bedaquiline.

The research processes focused on a neglected disease such as TB keep fulfilling the promise of more concise and secure treatment for the millions impacted globally," stated Dr. Rod Dawson, Principal Investigator for NC-009 and Managing Director & Head of the Clinical Research Unit at the University of Cape Town Lung Institute. "Objectives that once appeared entirely unattainable, such as the elimination of TB, are becoming more achievable due to innovations like sorfequiline and, previously, pretomanid. However, there is still much work to be done, and we must not cease until TB is no longer a danger.

The TB Alliance is enhancing collaborations with countries heavily affected by tuberculosis, including India, China, Indonesia, South Africa, and Brazil, in preparation for a Phase 3 clinical trial scheduled for 2026. This upcoming study presents a chance to gain approval for a new medication and treatment plan, as well as the initial step in creating an ultra-short treatment regimen. These partnerships are based on previous efforts in the development and implementation of BPaL-based regimens, aiming to simplify the process of creating new TB treatments and speed up the availability of better options for those affected by the disease.

The therapy was incredible. It was quicker and simpler than I had anticipated," said Thuto Pulane, a participant in the NC-009 clinical study. "I would advise anyone not to be scared. Tuberculosis treatment has advanced significantly, and this new research offers us even greater optimism.

Sorfequiline is available in tablet form, and SPaL will also serve as a fully oral treatment for tuberculosis. Alongside the upcoming SPaL Phase 3 trial, the TB Alliance intends to investigate administering a sorfequiline-based therapy as a long-acting injection (LAI), a method that might help shorten the treatment period to as little as one month.

For many years, the typical treatment duration for tuberculosis has been six months," stated Dr. Maria Beumont, Vice President and Chief Medical Officer at TB Alliance. "Using BPaL, we demonstrated that we can significantly simplify and reduce the length of treatment for drug-resistant TB, but this was only the initial step. With treatment plans currently being developed, we are confident that we can make treatment even shorter and simpler — for every type of TB. The findings from this study move us nearer to our objective and the ultimate elimination of TB as a worldwide health concern.

Background

TB is a challenging infection to treat, necessitating patients to use a combination of medications for a minimum of four to six months. Even once symptoms have gone away, treatment must continue to ensure that every trace of the disease is completely eliminated. The extent and severity of TB worldwide is largely driven by outdated and ineffective TB medications. New drug treatments are urgently required to manage the TB pandemic effectively.

The BPaL treatment — which includes the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L) — was initially tested in clinical trials by the TB Alliance. Pretomanid, as part of the BPaL regimen, received its initial regulatory approval in August 2019 for treating extremely drug-resistant forms of TB. This was the first time a TB medication developed by a non-profit organization received regulatory clearance. Before this, less than two-thirds of patients with drug-resistant TB were successfully treated. Available treatments were scarce, costly, harmful, and extended over long periods — often requiring patients to take more than 20 pills daily for 9 months to two years or longer. Following the approval, over 210,000 courses of pretomanid have been ordered worldwide, resulting in anApproximately 11,000 lives and $100 million USD have been saved worldwide..

Previously, in vitro studies showed that sorfequiline had anti-mycobacterial activity about 10 times higher than bedaquiline. In preclinical research, sorfequiline indicated a potential for greater safety compared to bedaquiline, with a lower risk of causing QT interval prolongation. In Phase 1 trials with 165 healthy participants, only a small number of generally mild adverse events were reported.

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