A new study demonstrates that the drug regimen consisting of glecaprevir plus pibrentasvir for non-cirrhotic patients with HCV genotype 1-6 is safe and effective.
The hepatitis C virus (HCV) is responsible for a tremendous disease burden; an estimated 71 million individuals are reported to have a chronic hepatitis infection. A large number of those chronically infected with HCV will develop liver cirrhosis or hepatocellular carcinoma. In fact, an estimated 400,000 individuals perish each year from the virus.
There are six HCV genotypes that have been shown to respond differently to treatment, with genotype 3 being the most difficult to treat. Direct-Acting Antiviral (DAA) therapy is the current gold standard of treatment for HCV, curing most HCV patients within 12 weeks or less. However, there is still a need for highly effective DAA therapy that targets all HCV genotypes with a shorter treatment duration and decreased likelihood of HCV resistance.
A new study published in the Journal of Hepatology by principal investigator Federico Mensa, MD, and his colleagues, examined the safety and efficacy of 8- as well as 12-week treatment regimens consisting of glecaprevir and pibrentasvir. The study was conducted in patients with chronic HCV, encompassing genotypes 1 to 6.
Glecaprevir targets the HCV non-structural protein 3/4A protease, while pibrentasvir is a HCV NS5A inhibitor. Patients from 80 sites in various locations, including the United States, were deemed eligible for the study if they were between the ages of 18 and 70, had non-cirrhotic chronic HCV genotypes 1-6 with elevated HCV RNA levels, and had never been treated with DAAs previously. Patients that were co-infected with HBV, HIV, or more than one genotype of HCV were excluded from the study.
The authors conducted two open-label, multi-center, phase 2 clinical studies; SURVEYOR-1 involved genotypes 1,4, 5, and 6, while SURVEYOR-II consisted of patients with HCV genotypes 2 and 3. The first part of each study involved administering various doses of glecaprevir and pibrentasvir for 12 weeks. The second part examined the efficacy of 300 mg of glecaprevir and 120 mg of pibrentasvir, once a day, for 8 weeks. The primary endpoint of the study was the percentage of patients who achieved sustained virologic response (SVR) at 12 weeks.
The study included 449 patients, of which 25% had HCV genotype 1, 29% had genotype 2, 39% had genotype 3, and 8% had genotypes 4 to 6. The 12-week treatment led to high SVR rates in all genotypes examined (97 to 100% for genotype 1, 96 to 100% for genotype 2, 83 to 94% for genotype 3, and 100% for genotypes 4 to 6). For the 8-week treatment, 97 to 98% achieved SVR with no reported virologic failures.
Overall, the study demonstrated that the drug regimen consisting of glecaprevir plus pibrentasvir is safe and efficacious. Dr. Mensa and his colleagues determined that this regimen can achieve high SVR rates in non-cirrhotic patients infected with various genotypes within 8 weeks. In addition, this combination can be taken once a day orally, which can be expected to increase patient adherence and tolerance to the regimen.
Future work will address the efficacy of glecaprevir plus pibrentasvir in patients with cirrhosis, as well as in patients co-infected with HBV, HIV, and multiple HCV genotypes.
Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.