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A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial

Medicine and Health

A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial

A. H. Diacon, C. E. B. Iii, et al.

A groundbreaking phase 2a trial evaluates ganfeborole's early bactericidal activity in treating untreated pulmonary tuberculosis. The study, conducted by a team including Andreas H. Diacon and Clifton E. Barry III, highlights promising results with significant reductions in sputum colony-forming units and demonstrates the drug's potential role in combination therapy.

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Playback language: English
Abstract
This phase 2a, single-center, open-label, randomized trial assessed the early bactericidal activity (EBA), safety, and pharmacokinetics of ganfeborole in participants with untreated, rifampicin-susceptible pulmonary tuberculosis. Ganfeborole (1/5/15/30 mg) or standard of care was administered daily for 14 days to 75 males. Numerical reductions in sputum colony-forming units were observed with 5, 15, and 30 mg ganfeborole. Adverse events were comparable across groups and grade 1 or 2. Post-hoc analysis of PET/CT scans showed treatment responses, and transcriptional analysis revealed an association with neutrophil-dominated modules at 30 mg. Ganfeborole shows potential for tuberculosis combination therapy.
Publisher
Nature Medicine
Published On
Mar 01, 2024
Authors
Andreas H. Diacon, Clifton E. Barry III, Alex Carlton, Ray Y. Chen, Matt Davies, Veronique de Jager, Kim Fletcher, Gavin C. K. W. Koh, Irina Kontsevaya, Jan Heyckendorf, Christoph Lange, Maja Reimann, Sophie L. Penman, Rhona Scott, Gareth Maher-Edwards, Simon Tiberi, Georgios Vlasakakis, Caryn M. Upton, David Barros Aguirre
Tags
ganfeborole
tuberculosis
bactericidal activity
sputum colony-forming units
safety
pharmacokinetics
clinical trial
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