Alpibectir TB Trial Results Published in NEJM; Phase 2b Begins
NEJM-published Phase 2a results show alpibectir enabled a two-thirds dose reduction of ethionamide and clinical proof of concept in pulmonary TB. First patient dosed in the Phase 2b STEP2C Stage 3 trial within UNITE4TB.
The New England Journal of Medicine has published results from a 7-day Phase 2a early bactericidal activity study, showing that alpibectir plus ethionamide (AlpE) established clinical proof of concept in pulmonary tuberculosis. In the trial, alpibectir enabled the ethionamide dose to be reduced by two thirds. At the same time, the first patient has been dosed in the STEP2C Stage 3 Phase 2b trial of AlpE within the international UNITE4TB platform.
In earlier clinical work, the alpibectir–ethionamide combination delivered a 7-day early bactericidal activity signal comparable to isoniazid and has been generally well tolerated across Phase 1/2 settings. The results, conducted in South Africa and now published in the New England Journal of Medicine, support further evaluation of AlpE as a bactericidal component within first-line and specialty TB regimens. AlpE pairs alpibectir (BVL-GSK098) with the established antibiotic ethionamide and is designed to overcome resistance and enhance ethionamide’s potency at lower doses. Ethionamide has been used to treat tuberculosis for decades, but dose-dependent toxic effects have limited its use; until now it has had to be taken in very high doses, often leading to severe side effects such as nausea and vomiting.
The Phase 2b study is sponsored by LMU University Hospital Munich and conducted across six African countries, aiming to enroll a total of 120 adult participants with drug-susceptible pulmonary tuberculosis (NCT05807399). The design adds AlpE to rifampicin, pyrazinamide, and ethambutol for two months, followed by 18 weeks of rifampicin and isoniazid alone. The trial targets dose finding, efficacy, safety, and pharmacokinetics and is slated to read out by year-end 2027. The two-month intensive phase is effectively isoniazid-sparing.
Pharmaceutical company GSK, whose active substance alpibectir is being investigated as an ethionamide booster, is involved in the study. A separate 14-day, open-label Phase 2a assessing AlpE with first-line TB drugs has completed enrollment, with top-line results due in Q2 2026. In parallel, BioVersys plans a Phase 2 study in TB meningitis in the first half of 2026. “With the evaluation of Alpibectir, UNITE4TB is testing its fifth novel drug candidate in its innovative phase IIb regimen selection platform, where we evaluate how novel assets are best combined with other licensed or new drugs. This approach will help to derisk the chance of progressing the wrong combination into phase III,” said the Scientific Director of UNITE4TB and Principal Investigator of the STEP2C Stage 3 study.
UNITE4TB brings together 30 partners from 13 countries with the aim of fundamentally improving the development of new tuberculosis treatment regimens through innovative trial designs, adaptive platform-trial approaches, and more efficient clinical processes.