A next-generation antibiotic, sorfequiline, has delivered encouraging results in a Phase II trial for treating drug-sensitive tuberculosis (TB). When paired with pretomanid and linezolid, the new diarylquinoline compound demonstrated superior efficacy compared to standard TB therapy, according to findings presented by TB Alliance at the Union World Conference on Lung Health in Denmark.
Sorfequiline (TBAJ-876) outperformed the conventional four-drug regimen of isoniazid, rifampin, pyrazinamide and ethambutol. Researchers also reported that it showed higher activity than treatment combinations using bedaquiline — the first approved next-generation diarylquinoline, introduced in 2012 for multidrug-resistant TB.
Bedaquiline has played a key role in reducing treatment duration for drug-resistant TB to around six months, similar to the standard timeline for drug-sensitive TB, through the BPaL regimen (bedaquiline, pretomanid and linezolid). The latest study evaluated sorfequiline at three doses — 25 mg, 50 mg and 100 mg — in combination with pretomanid and linezolid, alongside comparisons to BPaL and the standard therapy.
The primary outcome measured was time to stable sputum conversion (SSC) by week 8. SSC was achieved by 59% of participants in the 100 mg sorfequiline group, compared to 45% in both the BPaL group and the standard treatment arm. Notably, 64% of those receiving the highest sorfequiline dose were able to discontinue treatment by week 15 after achieving negative sputum results at week 8.
Early data suggest sorfequiline may offer safety advantages over bedaquiline, showing lower cardiac toxicity signals and improved patient tolerance. Like bedaquiline, the drug is designed for oral administration, supporting easier adherence over extended treatment periods.
TB Alliance is preparing to advance sorfequiline into Phase III trials and is simultaneously exploring a long-acting injectable option that could potentially shorten TB treatment to as little as one month.
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