The combination of glecapravir/pibrentasvir (G/P) has demonstrated high efficacy in patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection who experienced previous treatment failure with sofosbuvir plus a nonstructural protein 5A (NS5A) inhibitor, according to a phase 3b multicenter open label study published in Gastroenterology.
While the development of direct-acting antiviral agents has revolutionized hepatitis C treatment, treatment options are limited for patients who do not respond to treatment with sofosbuvir plus an NS5A inhibitor. Options for salvage therapy are limited because resistance-associated substitutions (RASs) to NS5A inhibitors are selected in most if not all patients who do not achieve a sustained virologic response (SVR) after treatment with regimens that included an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients; therefore, researchers performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P with and without ribavirin in 177 patients with HCV GT1 infection with lack of response to treatment with sofosbuvir and an NS5A inhibitor.
Patients without cirrhosis received G/P for 12 weeks (n=78, group A) or 16 weeks (n=49, group B) and patients with compensated cirrhosis received G/P and ribavirin for 12 weeks (n=21, group C) or G/P for 16 weeks (n=29, group D). The researchers found that the percentage of patients with an SVR 12 weeks after treatment (SVR12) in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. G/P was well tolerated and ribavirin increased adverse events but did not increase efficacy.
“In summary, our study provided additional safety and efficacy data in support of the use of 16-week G/P in HCV GT1 patients (with or without compensated cirrhosis) who failed prior treatment with sofosbuvir and NS5A inhibitor,” stated the investigators.
Lok AS, Sulkowski MS, Kort JJ, et al. Efficacy of glecaprevir and pibrentasvir in patients with genotype 1 hepatitis C virus infection with treatment failure after NS5A inhibitor plus sofosbuvir therapy [published online August 8, 2019]. Gastroenterology. doi:10.1053/j.gastro.2019.08.008