Lucia Rose1, Tiffany E Bias2, Clinton B Mathias3, Stacey B Trooskin4, Jeffrey J Fong5. 1. Western New England University, Springfield, MA, USA lrose@wne.edu. 2. Hahnemann University Hospital, Philadelphia, PA, USA. 3. Western New England University, Springfield, MA, USA. 4. Drexel University College of Medicine, Philadelphia, PA, USA. 5. MCPHS University-Worcester/Manchester, Worcester, MA, USA.
Abstract
OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..
OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..
Authors: Matteo Castelli; Nicola Clementi; Giuseppe A Sautto; Jennifer Pfaff; Kristen M Kahle; Trevor Barnes; Benjamin J Doranz; Matteo Dal Peraro; Massimo Clementi; Roberto Burioni; Nicasio Mancini Journal: Drug Discov Today Date: 2014-08-27 Impact factor: 7.851
Authors: Albert Do; Yash Mittal; AnnMarie Liapakis; Elizabeth Cohen; Hong Chau; Claudia Bertuccio; Dana Sapir; Jessica Wright; Carol Eggers; Kristine Drozd; Maria Ciarleglio; Yanhong Deng; Joseph K Lim Journal: PLoS One Date: 2015-08-27 Impact factor: 3.240