P091
The novel combination alpibectir/ethionamide (AlpE) is active on drug-sensitive and drug-resistant clinical isolates of Mycobacterium tuberculosis
L Hofmann(1) N Willand(3) G E Dale(1,2) A Baulard(4) M Pieren(2)
1:Bioversys SAS; 2:Bioversys AG; 3:Univ. Lille, Inserm, Institut Pasteur de Lille, Lille, France; 4:Univ. Lille, CNRS, Inserm, Institut Pasteur de Lille, Lille, France
Tuberculosis (TB) is one of the world’s top infectious disease killer. It is estimated that 10.6 million people developed TB in 2022, and despite being a preventable and curable disease, 1.3 million died from it. Over the last decades, treatments for TB have improved in efficacy, toxicity and length duration with the WHO new recommendation for drug-susceptible TB being a 4-drug cocktail (isoniazid (INH), rifapentine, moxifloxacin and pyrazinamide) for 4 months. Meanwhile, antimicrobial resistance (AMR) is increasing, and it is estimated that, in 2022, 410 000 people developed MDR (multidrug-resistant)/RR (rifampicin-resistant)-TB. The current treatment for MDR/RR-TB is a combination of bedaquiline, pretomanid, linezolid and moxifloxacin (BPaL±M, 6 months) but many patients developed severe adverse effects (AEs) associated to the long-term administration of linezolid, reinforcing the need for new medications.
Developed by BioVersys, GSK, The Pasteur Institute Lille and Lille University, the clinical candidate alpibectir is a new chemical potentiator of ethionamide (Eto), a pro-drug used in MDR-TB for decades. Alpibectir enhances the activation of Eto in its active form allowing for a safer and better tolerated dose of Eto.
AlpE, the combination of alpibectir and Eto, is rapidly bactericidal, active on drug-susceptible and MDR-TB isolates. AlpE keeps robust activity against Eto-resistant, INH-resistant and MDR strains. AlpE is also active on bedaquiline and pretomanid-resistant strains. AlpE emerges as a promising candidate for an essential companion drug to treat INH mono-resistant and MDR-TB patients.