In a new study published in the New England Journal of Medicine, lead investigator Marc Bourliere, MD, from the Hospital Saint Joseph in Marseilles, and his colleagues conducted 2 phase 3 clinical trials to explore treatment options for those chronically infected with hepatitis C (HCV) who have had no success with direct-acting antiviral therapy (DAA) therapy.
HCV is the causative agent of hepatitis and can result in both acute as well as chronic infections. In those infected with HCV, 15 to 45% will develop an acute infection which may clear within 6 months without treatment. However, 55% to 85% of HCV-infected patients will develop a chronic HCV infection. The World Health Organization estimates that 71 million people are currently infected with HCV. Treatment with highly effective DAA is now the standard of care for HCV. Treatment with DAAs has been shown to be very efficacious, leading to a sustained viral response (SVR) in most patients. However, for patients that do not respond positively to treatment with DAAs, there is currently no approved retreatment option.
Dr. Bourliere et al’s first trial, POLARIS-1, involved 300 patients with HCV genotype 1 who had previously received a drug combination containing an NS5A inhibitor. Half of the patients received a combination of sofosbuvir, a nucleotide polymerase inhibitor, velpatasvir, an NS5A inhibitor, and voxilaprevir, a protease inhibitor, once a day for 3 months. The remaining 150 patients received a placebo for the same period.
In the second clinical trial, POLARIS-4, patients with HCV genotypes 1, 2 or 3 who had been given a DAA regimen without an NS5A inhibitor were assigned to either receive a 3-drug cocktail, consisting of sofosbuvir, velpatasvir, and voxilaprevir, or a 2-drug cocktail, only consisting of sofosbuvir and velpatasvir, for 12 weeks.
In POLARIS-1, the results were very promising, with 96% of the patients receiving sofosbuvir, velpatasvir, and voxilaprevir achieving SVR. This is compared to 0% of patients achieving SVR in the placebo group. In POLARIS-4, 98% of patients receiving the 3-drug cocktail achieved SVR while 90% of those receiving only sofosbuvir and velpatasvir achieved SVR. The authors note that the most common side effects of the therapy were fatigue, nausea, diarrhea, and headaches. However, less than 1% of patients discontinued treatment due to the severity of the side effects.
Overall, Dr. Bourliere and his colleagues conclude that administering sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks to patients who had previously failed treatment with DAAs resulted in high SVR rates. This study provides hope to those who have not had success with DAA therapy. Dr. Bourliere is quoted in a press release as saying, “we have other options even if you fail the first treatments.”
The data from POLARIS-1 and POLARIS-4 are in the process of being approved by the US Food and Drug Administration (FDA). Although this work has the potential to change the landscape of HCV therapy, the new pill, made by Gilead Sciences, could be very pricey, potentially costing patients approximately $100,000 for the full 12-week treatment regimen.
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.