High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1-6 patients without cirrhosis

J Hepatol. 2018 Aug;69(2):293-300. doi: 10.1016/j.jhep.2018.03.007. Epub 2018 Mar 16.

Abstract

Background & aims: Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed.

Methods: Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1-6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate.

Results: The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare.

Conclusions: G/P therapy for eight weeks in patients with chronic HCV GT 1-6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks.

Lay summary: In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1-6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.

Keywords: Direct-acting antiviral; Hepatitis C; Pangenotypic; Short duration.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Benzimidazoles / therapeutic use*
  • Female
  • Genotype
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / virology
  • Humans
  • Male
  • Middle Aged
  • Quinoxalines / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Sustained Virologic Response*
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • glecaprevir