MSD announces positive results from elbasvir/grazoprevir HCV study

MSD has announced results from the Phase III C-EDGE: Head-to-head  trial evaluating the efficacy and safety of the investigational once-daily, fixed-dose combination tablet elbasvir/grazoprevir versus a regimen of sofosbuvir plus peginterferon and ribavirin (pegIFN/RBV) in treatment-naïve and pegIFN/RBV treatment-experienced patients with chronic hepatitis C (HCV) genotype (GT) 1 or GT4 infection.

In this study, elbasvir/grazoprevir demonstrated superiority on efficacy and improvement on safety endpoints compared to sofosbuvir plus pegIFN/RBV, based on pre-specified analyses. In the full analysis set, the efficacy endpoint of sustained virologic response (SVR) 12 weeks after the completion of therapy (SVR12, considered virologic cure) was achieved in 99% of patients receiving elbasvir/grazoprevir for 12 weeks versus 90% of patients receiving sofosbuvir plus pegIFN/RBV for 12 weeks. 

Commenting on the results, Dr Jan Sperl, Department of Hepatogastroenterology, Institute for Clinical and Experimental Health, Prague, Czech Republic and lead study investigator, said: “Overall in this study, the elbasvir/grazoprevir regimen showed superior SVR rates and improvement on pre-specified safety endpoints compared to the sofosbuvir plus peginterferon and ribavirin regimen in these genotype 1- or 4-infected patients. Sofosbuvir in combination with peginterferon and ribavirin continues to be a prescribed treatment regimen in many regions, and this comparative study versus combination treatment with elbasvir/grazoprevir provides interesting and important insights.”

Tier 1 AEs lower in the elbasvir/grazoprevir treatment group

The primary safety analysis of the trial compared the incidence of adverse events (AEs) of special relevance (Tier 1 AEs) between the elbasvir/grazoprevir and sofosbuvir plus pegIFN/RBV treatment groups. Additional AEs (Tier 2 AEs) also were recorded. Overall, the incidence of Tier 1 AEs, including those commonly associated with pegIFN and/or RBV such as haematological side effects of decreased haemoglobin and decreased neutrophil count, were lower in the elbasvir/grazoprevir treatment group versus the sofosbuvir plus pegIFN/RBV treatment group. In the elbasvir/grazoprevir treatment group, headache was the only AE reported at a frequency of greater than 10%. In the sofosbuvir plus pegIFN/RBV treatment group, AEs reported in greater than 10% of patients were pyrexia, headache, fatigue, asthenia, influenza-like illness, chills, myalgia, decreased appetite, anaemia, nausea and cough. No grade three or four abnormalities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or haemoglobin were observed in the elbasvir/grazoprevir group. In the sofosbuvir plus pegIFN/RBV group, one patient had a grade three ALT abnormality and five patients had grade three or four haemoglobin reduction.

“Treatment regimens containing peginterferon and ribavirin are associated with certain serious side effects,” said Dr Jan Gerstoft, Clinic for Infectious Diseases and Rheumatology, Denmark. “This study provides evidence for the clinical potential of elbasvir/grazoprevir in chronic HCV genotype 1- or 4-infection as compared with a regimen containing peginterferon and ribavirin along with sofosbuvir.”

Elbasvir/grazoprevir tablets were approved for use with or without ribavirin for treatment of chronic HCV genotypes 1 or 4 infection in adults, based in part on prior studies from the Phase III programme, by the US Food and Drug Administration and Health Canada in January 2016, and by Swissmedic in April 2016.  Marketing applications for combination therapy with elbasvir and grazoprevir are currently under regulatory review in other countries around the world, including the EU and Japan. The drug combination is not currently licensed in the UK.