Advertisement

Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis

Published:April 13, 2017DOI:https://doi.org/10.1016/j.jhep.2017.03.039

      Highlights

      • An all oral, once-daily, RBV-free, pangenotypic HCV treatment option is described.
      • 8- or 12-week treatment with glecaprevir + pibrentasvir yielded high rates of SVR12.
      • Treatment was well-tolerated with a favorable safety profile.

      Background & Aims

      Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4 A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1–6 infection.

      Methods

      SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1–6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12 weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12).

      Results

      Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4–6 infection, respectively. Twelve-week treatment achieved SVR12 in 97–100%, 96–100%, 83–94%, and 100% in genotypes 1, 2, 3, and 4–6, respectively. Eight-week treatment with 300 mg glecaprevir plus 120 mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97–98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed.

      Conclusions

      Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1–6-infected patients without cirrhosis following 8- or 12-week treatment durations.

      Lay summary

      The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1–6 infection. This article describes results from two phase II trials investigating a range of doses at treatment durations of 8 or 12 weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well tolerated and significant laboratory abnormalities were rare.
      Clinical trial registration: clinicaltrials.gov Identifiers: NCT02243280 and NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280, http://www.clinicaltrials.gov/show/NCT01939197.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Razavi H.
        • Waked I.
        • Sarrazin C.
        • et al.
        The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.
        J Viral Hepatitis. 2014; 21: 34-59
        • Messina J.P.
        • Humphreys I.
        • Flaxman A.
        • et al.
        Global distribution and prevalence of hepatitis C virus genotypes.
        Hepatology. 2015; 61: 77-87
        • Gower E.
        • Estes C.
        • Blach S.
        • Razavi-Shearer K.
        • Razavi H.
        Global epidemiology and genotype distribution of the hepatitis C virus infection.
        J Hepatol. 2014; 61: S45-S57
        • Ampuero J.
        • Romero-Gomez M.
        • Reddy K.R.
        Review article: HCV genotype 3 - the new treatment challenge.
        Aliment Pharmacol Ther. 2014; 39: 686-698
        • Sciences G.
        EPCLUSA (sofosbuvir and velpatasvir) [package insert].
        Foster City, CA2016
        • Asselah T.
        • Boyer N.
        • Saadoun D.
        • Martinot-Peignoux M.
        • Marcellin P.
        Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives.
        Liver Int. 2016; 36: 47-57
        • Pawlotsky J.M.
        New hepatitis C therapies: the toolbox, strategies, and challenges.
        Gastroenterology. 2014; 146: 1176-1192
        • Zeuzem S.
        • Ghalib R.
        • Reddy K.R.
        • et al.
        Ann Intern Med. 2015; https://doi.org/10.7326/M7315-0785
        • Younossi Z.M.
        • Kanwal F.
        • Saab S.
        • et al.
        The impact of hepatitis C burden: an evidence-based approach.
        Aliment Pharmacol Ther. 2014; 39: 518-531
        • Lawitz E.J.
        • O'Riordan W.D.
        • Asatryan A.
        • et al.
        Potent antiviral activities of the direct-acting antivirals ABT-493 and ABT-530 with three-day monotherapy for hepatitis C virus genotype 1 infection.
        Antimicrob Agents Chemother. 2015; 60: 1546-1555
        • Ng T.
        • Krishnan P.
        • Pilot-Matias T.
        • et al.
        In vitro antiviral activity and resistance profile of the next generation hepatitis C virus NS5A inhibitor pibrentasvir.
        Antimicrob Agents Chemother. 2017;
        • Gane E.
        • Poordad F.
        • Wang S.
        • et al.
        High efficacy of ABT-493 and ABT-530 in patients with HCV genotype 1 or 3 infection and compensated cirrhosis.
        Gastroenterology. 2016;
        • Lawitz E.J.
        • O'Riordan W.D.
        • Asatryan A.
        • et al.
        Potent antiviral activity of direct-acting antivirals, ABT-493 and ABT-530, with 3-day monotherapy for hepatitis C genotype 1 infection.
        Antimicrob Agents Chemother. 2015;
        • Wang C.
        • Jia L.
        • O'Boyle 2nd, D.R.
        • et al.
        Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity.
        Antimicrob Agents Chemother. 2014; 58: 5155-5163
      1. OLYSIO (simeprevir) [package insert]. Janssen Therapeutics. Titusville, NJ2013.

        • Cheng G.
        • Tian Y.
        • Doehle B.
        • et al.
        In vitro antiviral activity and resistance profile characterization of the hepatitis C virus NS5A inhibitor ledipasvir.
        Antimicrob Agents Chemother. 2016; 60: 1847-1853
        • Hernandez D.
        • Zhou N.
        • Ueland J.
        • Monikowski A.
        • McPhee F.
        Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors.
        J Clin Virol. 2013; 57: 13-18
        • Liu R.
        • Curry S.
        • McMonagle P.
        • et al.
        Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvir.
        Antimicrob Agents Chemother. 2015; 59: 6922-6929
      2. Administration FaD. Division of Antiviral Products Virology Review, NDA 208341. 2015.

        • Krishnan P.
        • Beyer J.
        • Mistry N.
        • et al.
        In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of HCV NS5A.
        Antimicrob Agents Chemother. 2014;
        • Muir A.J.
        • Strasser S.
        • Wang S.
        • Shafran S.
        • Bonacini M.
        • Kwo P.
        • et al.
        High SVRRates with ABT-493 + ABT-530 co-administered for 8 weeks in non-cirrhotic patients with HCV genotype 3 infection.
        Hepatology. 2016; 64: 183-212
      3. Hassanein T, Wyles, D., Wang, S. et al. Glecaprevir/Pibrentasvir Demonstrates High SVR Rates in Patients with HCV Genotype 2, 4, 5, or 6 Infection without Cirrhosis Following an 8-Week Treatment Duration: SURVEYOR-II, Part 4.). Paper presented at: The Liver Meeting 2016; Boston, MA.