ABSTRACT
INTRODUCTION: Glecaprevir (formerly ABT-493, pangenotypic NS3/4A protease inhibitor) and pibrentasvir (formerly ABT-530, pangenotypic NS5A inhibitor) are second generation direct acting antivirals (DAA) for the treatment of chronic Hepatitis C (HCV). It is a fixed dose ribavirin (RBV)-free regimen with activity against genotypes (GT) 1-6. In vitro the two antivirals have synergistic activity with a high barrier to resistance and potent activity against common polymorphisms. It is once daily oral dosing with minimal absorption, primary biliary excretion, and negligible renal excretion, making it safe for patients with renal impairment. This regimen is being reviewed because it is the first pangenotypic regimen suitable for those with renal impairment and prior DAA failure. Areas covered: The key phase 2 and 3 trials which investigated the efficacy and safety of glecaprevir/pibrentasvir are reviewed by methodology, primary end point, baseline demographic data, response rates, and adverse events. Literature search methodology involved reviewing key abstracts presented at the American Association for the Study of Liver Disease and European Association for the Study of Liver. Expert commentary: The advantages and limitations of glecaprevir/pibrentasvir will be reviewed in comparison to its competitor drug on the market.
Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Enzyme Inhibitors/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Quinoxalines/therapeutic use , Sulfonamides/therapeutic use , Aminoisobutyric Acids , Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , Benzimidazoles/adverse effects , Benzimidazoles/pharmacokinetics , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/metabolism , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Cyclopropanes , Drug Combinations , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/pharmacokinetics , Genotype , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Intracellular Signaling Peptides and Proteins , Lactams, Macrocyclic , Leucine/analogs & derivatives , Proline/analogs & derivatives , Pyrrolidines , Quinoxalines/adverse effects , Quinoxalines/pharmacokinetics , Sulfonamides/adverse effects , Sulfonamides/pharmacokinetics , Treatment Outcome , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolismABSTRACT
The treatment of chronic hepatitis C virus (HCV) has undergone a period of rapid evolution. The era of combination direct antivirals has led to high rates of sustained viral response (SVR), limited toxicities, and more broad applicability across patient demographics. Even current therapies have their limitations, however, including genotype specificity and variable durations of treatment depending on the presence or absence of cirrhosis. Developing a fixed-duration pangenotypic regimen that can broadly treat all stages of fibrosis with equal rates of SVR in all patients, irrespective of treatment experience, is the goal of future therapies. This article reviews antivirals in development.
