Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants.

Abstract

A combination of nucleotide hepatitis C virus (HCV) nonstructural protein (NS) 5B and 5A inhibitors is a preferred standard of care for treating chronic HCV. Bemnifosbuvir is a novel oral guanosine nucleotide prodrug with potent pan-genotypic inhibitory activity against HCV NS5B. Ruzasvir, a small-molecule NS5A inhibitor, has demonstrated improved anti-HCV activity compared with first-generation NS5A inhibitors. Clinical studies have demonstrated favorable efficacy and safety of bemnifosbuvir and ruzasvir in combination with other NS5A and NS5B inhibitors, respectively. A Phase 1 study in healthy participants was conducted to assess the drug-drug interaction potential between bemnifosbuvir and ruzasvir, as well as food effects following coadministration of both compounds. Under fasted conditions, the peak, trough, and total exposure to bemnifosbuvir and its metabolites were increased upon coadministration with ruzasvir (by a maximum of 33% vs bemnifosbuvir alone), whereas the corresponding values for ruzasvir were decreased upon coadministration with bemnifosbuvir (by a maximum of 26% vs ruzasvir alone). Food delayed peak exposure to both drugs (by up to 2 hours) while increasing their peak and total exposure by up to 63%. No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV.