Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials

Ann Hepatol. May-Jun 2016;15(3):333-49. doi: 10.5604/16652681.1198803.

Abstract

Introduction & aim: Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection.

Material and methods: Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12).

Results: SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively.

Conclusion: Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism
  • Clinical Trials, Phase III as Topic
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Hepacivirus / genetics
  • Hepatitis C / blood
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Intracellular Signaling Peptides and Proteins
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • RNA, Viral / blood
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • Biomarkers
  • Carrier Proteins
  • Interferon-alpha
  • Intracellular Signaling Peptides and Proteins
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Oligopeptides
  • Protease Inhibitors
  • RNA, Viral
  • Recombinant Proteins
  • Thiazoles
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • faldaprevir
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT01297270
  • ClinicalTrials.gov/NCT01343888