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isoniazid + rifampicin + pyrazinamide + ethambutol + alpibectir + ethionamide
- Development stage
- Phase 2
- Lead developer
- BioVersys
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This is a six-drug combination therapy being investigated for the treatment of tuberculosis meningitis (TBM). It consists of the standard four-drug first-line tuberculosis regimen (HRZE: isoniazid, rifampicin, pyrazinamide, and ethambutol) supplemented with AlpE, a novel potentiator-antibiotic combination. AlpE contains alpibectir (BVL-GSK098), a small molecule transcriptional regulatory inhibitory compound (TRIC), and ethionamide. Alpibectir acts by inhibiting EthR, a repressor of the EthA enzyme required to activate ethionamide, thereby significantly increasing ethionamide's potency and allowing for lower, less toxic doses. The specific AlpE625 designation refers to a dose of 625 mg of ethionamide paired with alpibectir. This regimen is currently in Phase 2a clinical trials to evaluate its safety, pharmacokinetics in plasma and cerebrospinal fluid, and efficacy in patients with TBM.
- Other names
- HRZE + AlpE625HRZE plus AlpE625
02
Targets
EmbA-EmbB (Arabinosyltransferase EmbA-EmbB complex)EmbC (Mycobacterium avium complex arabinosyltransferase EmbC)EthR;EthR2 (EthR/EthR2)Aspartate decarboxylaseembB (Arabinosyltransferase EmbB)rpoB (DNA-directed RNA polymerase subunit beta)InhAPncA (Nicotinamidase)
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