Novel 4-Month Pan-TB Regimens Show Promise for Lung Function Recovery

A novel 4-month pan-tuberculosis (TB) regimen containing the investigational oxazolidinone sutezolid and N-acetylcysteine (NAC) demonstrated encouraging lung function recovery and fewer adverse events than standard therapy in preliminary phase 2c findings presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando, Florida.

In an interview at ATS 2026, Robert Wallis, MD, the chief science officer at
the Aurum Institute & professor of medicine at Vanderbilt University, discussed how the PanTB-HM trial was designed to address 2 major unmet needs in global TB care: the need for a “pan-TB” regimen that can be used without rifampin susceptibility testing and the long-term pulmonary damage that persists after microbiologic cure.

“We hope to tackle 2 problems with this strategy,” Wallis said. “One of them is the pan-TB angle, and the other is the lung function recovery angle.”

The phase 2c PanTB-HM trial evaluated 3 investigational 4-month regimens against standard 6-month HRZE therapy in adults with culture-confirmed rifampin-susceptible pulmonary TB. Experimental regimens combined sutezolid, bedaquiline, and pretomanid, with 1 arm additionally receiving NAC 1800 mg twice daily.

Among 378 participants, the mean baseline forced expiratory volume in 1 second (FEV1) was 72% predicted. Investigators reported 334 adverse events in the HRZE control arm compared with 212 to 221 adverse events across the experimental groups. Serious adverse events potentially attributable to treatment occurred more frequently in the control arm than in investigational arms, and investigators noted no typical oxazolidinone-associated serious adverse events.

The most notable findings involved lung function recovery in participants with impaired baseline pulmonary function, defined as FEV1 ≤ 62% predicted. Linear mixed-effects modeling demonstrated superior FEV1 recovery during the first 14 days among participants receiving the S1600BPN regimen containing NAC compared with HRZE (P =.004). Investigators observed a 10.6-point difference in FEV1 at day 14 versus standard therapy (P =.003), with the improvement largely maintained through day 168.

Wallis said the pulmonary recovery signal may have substantial implications, given growing recognition that many patients discharged as “cured” continue to experience chronic respiratory morbidity.

“Only within the past several years has it come to everyone’s realization that when we discharge someone from the TB clinic and say they’re cured, they’re not,” Wallis said. “At least half have bronchiectasis or fibrosis or cavities.”

He explained that post-TB lung disease contributes to recurrent infections, progressive airway damage, and shortened survival. According to Wallis, observational analyses suggest mortality risk after TB remains approximately 3-fold greater than expected, with reduced FEV1 appearing closely associated with long-term outcomes.

The rationale for NAC centers on oxidative lung injury. Wallis described how reactive oxygen species generated during pulmonary infection may damage mammalian airways and lung tissue despite limited effectiveness against Mycobacterium tuberculosis. NAC serves as a precursor to glutathione, a sulfur-containing antioxidant molecule depleted during prolonged TB infection and malnutrition.

“Our objective is that if glutathione is going to protect the lung in TB, then getting cysteine to help support glutathione synthesis is really critical,” Wallis said. “The easy way to do that is with NAC and acetylcysteine.”

He noted NAC is inexpensive, widely available, and already used clinically to prevent acetaminophen-induced liver injury, making it an appealing adjunctive therapy candidate in resource-limited settings.

Wallis also suggested sutezolid itself may contribute to pulmonary recovery through anti-inflammatory effects. Experimental arms containing sutezolid but not NAC showed intermediate improvements in lung function, raising the possibility that the agent modulates phagocytic cell inflammatory responses in addition to antimicrobial activity.

Although relapse data remain preliminary, as of January 2026, investigators reported 5 relapses in the S1200BP arm, 11 in the S1600BP arm, 6 in the S1600BPN arm, and 6 in the HRZE arm.

Investigators concluded the novel 4-month regimens “appear poised to meet WHO target regimen profiles for a pan-TB indication and to provide the additional benefit of superior recovery of lung function.”

Editor’s note: A relevant disclosure for Wallis includes Otsuka Pharmaceutical Development & Commercialization.

References

Wallis R, Mudzengi D, Mashatole S, et al. (Poster Board # P558) Novel 4-month Pan-TB Regimens Promoting Recovery of Lung Function: Preliminary Findings of the PanTB-HM Phase 2c Trial. Poster presented at ATS 2026 on May 17.