The once-daily, fixed-dose combination tablet elbasvir/grazoprevir (50 mg/100 mg) is more effective and safer than a commonly used regimen that includes sofosbuvir (400 mg) plus peginterferon and ribavirin in patients with chronic hepatitis C virus genotype 1 or genotype 4 infection, according to the results of a phase 3 trial released at the International Liver Congress 2016.
In the multi-center C-EDGE Head-to-Head study, investigators randomized 255 patients to 12 weeks of treatment with elbasvir (an NS5A inhibitor) plus grazoprevir (an NS3/4A protease inhibitor) or the NS5A inhibitor sofosbuvir plus peginterferon and ribavirin (PR).
The sofosbuvir plus PR regimen was recommended in guidelines at the start of the trial.
The study enrolled treatment-naive and PR treatment-experienced patients, with or without cirrhosis, with chronic hepatitis C virus (HCV) genotype (GT) 1 or GT4 infection.
“While direct-acting antiviral agents represent the standard-of-care treatment for HCV infection, head-to-head studies have not been reported,” said principal investigator Dr. Jan Sperl, who is a liver specialist at the Institute for Clinical and Experimental Health in Prague, Czech Republic.
“The addition of sofosbuvir to a peginterferon/ribavirin backbone has been shown to improve standard virologic response rates compared to PR alone, however, it retained the unfavorable safety profile of PR,” she added.
Results in the full analysis set showed that the primary efficacy endpoint of sustained virologic response 12 weeks after the completion of therapy (SVR12) was achieved in 99% (128/129) of patients receiving elbasvir/grazoprevir versus 90% (114/126) of patients receiving sofosbuvir plus PR.
Further analysis demonstrated superior SVR rates with the elbasvir/grazoprevir regimen in patients who had not responded to prior peginterferon/ribavirin therapy and in patients with cirrhosis, a higher baseline viral load, or IL28B non-CC genotype.
No patient had virologic failure in the elbasvir/grazoprevir group. However, virologic failure was documented in 11 (9%) patients in the sofosbuvir plus PR group.
Tier 1 adverse events occurred in 1% of the elbasvir/grazoprevir cohort, versus 28% of the sofosbuvir plus PR group. In the elbasvir/grazoprevir group, headache was the only adverse event documented in more than 10% of patients.
In the sofosbuvir plus PR group, adverse events reported in greater than 10% of patients included pyrexia, headache, fatigue, asthenia, influenza-like illness, chills, myalgia, decreased appetite, anemia, nausea and cough.
No grade 3 or 4 abnormalities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or hemoglobin were observed in the elbasvir/grazoprevir group. One patient in the sofosbuvir plus peginterferon/ribavirin group had a grade 3 ALT abnormality, and five patients had grade 3 or 4 hemoglobin reduction.
Elbasvir/grazoprevir is approved in the US, Canada and Switzerland for the treatment of patients with HCV genotype 1 or 4 infection and is under regulatory review in Europe, Japan and other countries.
The study was conducted at multiple sites in the European Union, Norway and Turkey.