sanfetrinem cilexetil (GV118819) / GSK - LARVOL DELTA

Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis. (PubMed, Drug Resist Updat) - P2 | "Preclinical in vitro and in vivo studies demonstrated that: (i) media composition impacts the activity of sanfetrinem against Mtb, being more potent in the presence of physiologically relevant cholesterol as the only carbon source, compared to the standard broth media; (ii) sanfetrinem shows broad spectrum activity against Mtb clinical isolates, including MDR/XDR strains; (iii) sanfetrinem is rapidly bactericidal in vitro against Mtb despite being poorly stable in the assay media; (iv) there are strong in vitro synergistic interactions with amoxicillin, ethambutol, rifampicin and rifapentine and, (v) sanfetrinem cilexetil is active in an in vivo model of infection. These data, together with robust pre-clinical and clinical studies of broad-spectrum carbapenem antibiotics carried out in the 1990s by GSK, identified sanfetrinem as having potential for treating TB and catalyzed a repurposing proof-of-concept Phase 2a clinical study (NCT05388448) in South Africa."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

EBA, Safety and Tolerability of Sanfetrinem Cilexetil (clinicaltrials.gov) - P2 | N=54 | Completed | Sponsor: TASK Applied Science | Recruiting ➔ Completed | N=105 ➔ 54 | Trial completion date: Dec 2023 ➔ Aug 2024 | Trial primary completion date: Sep 2023 ➔ Aug 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis. (PubMed, bioRxiv) - P2 | "Preclinical in vitro and in vivo studies demonstrated that: (i) media composition impacts the activity of sanfetrinem against Mtb , being more potent in the presence of physiologically relevant cholesterol as the only carbon source, compared to the standard broth media; (ii) sanfetrinem shows broad spectrum activity against Mtb clinical isolates, including MDR/XDR strains; (iii) sanfetrinem is rapidly bactericidal in vitro against Mtb despite being poorly stable in the assay media; (iv) there are strong in vitro synergistic interactions with amoxicillin, ethambutol, rifampicin and rifapentine and, (v) sanfetrinem cilexetil is active in an in vivo model of infection. These data, together with robust pre-clinical and clinical studies of broad-spectrum carbapenem antibiotics carried out in the 1990s by GSK, identified sanfetrinem as having potential for treating TB and catalyzed a repurposing proof-of-concept Phase 2a clinical study ( NCT05388448 ) currently underway..."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Carbapenem Antibiobics: Recent Update On Synthesis And Pharmacological Activities. (PubMed, Curr Drug Res Rev) - "Right from the breakthrough of carbapenems since 1976, many schemes on synthesis, structure-activity relationship (SAR), and biological activities have been carried out, and several carbapenems have been developed, including parentally active carbapenems like imipenem, doripenem, biapenem, meropenem, ertapenem, panipenem, razupenem, tomopenem, cilastatin, whereas orally active carbapenems like GV-118819, GV-104326, CS-834, L-084, DZ-2640, CL 191, 121, L-646, 591, S-4661, ER-35768, MK-826. The Witting reaction, Mitsunobu reaction, Dieckmann reaction, palladium-catalyzed hydrogenolysis, E. coli-based cloned synthesis, and biosynthetic enzymes such as carbapenem synthetase (carA), carboxymethylproline synthase (carB), carbapenem synthase (carC). Carbapenems are biologically in infections like urinary tract infections, bloodstream infections, tuberculosis, intra-abdominal infections, and pathogens like anaerobes, gram-positive and gram-negative bacteria."

Journal • Infectious Disease • Nephrology • Pulmonary Disease • Respiratory Diseases • Tuberculosis

EBA, Safety and Tolerability of Sanfetrinem Cilexetil (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: TASK Applied Science

New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis