Paul Y Kwo1, Fred Poordad2, Armen Asatryan3, Stanley Wang3, David L Wyles4, Tarek Hassanein5, Franco Felizarta6, Mark S Sulkowski7, Edward Gane8, Benedict Maliakkal9, J Scott Overcash10, Stuart C Gordon11, Andrew J Muir12, Humberto Aguilar13, Kosh Agarwal14, Gregory J Dore15, Chih-Wei Lin3, Ran Liu3, Sandra S Lovell3, Teresa I Ng3, Jens Kort3, Federico J Mensa3. 1. Stanford University Division of Gastroenterology and Hepatology, Palo Alto, CA, USA. Electronic address: pkwo@stanford.edu. 2. Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA. 3. AbbVie Inc., North Chicago, Illinois, USA. 4. University of Colorado School of Medicine, Denver, Colorado, USA. 5. Southern California GI and Liver Centers and Southern California Research Center, Coronado, California, USA. 6. Private Practice, Bakersfield, California, USA. 7. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 8. University of Auckland, Auckland, New Zealand. 9. University of Rochester Medical Center, Rochester, New York, USA. 10. eStudySite, San Diego, California, USA. 11. Henry Ford Health System, Detroit, Michigan, USA. 12. Duke University School of Medicine, Durham, NC, USA. 13. Louisiana Research Center, Shreveport, LA, USA. 14. Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK. 15. Kirby Institute, UNSW Sydney, and St. Vincent's Hospital, Sydney, NSW, Australia.
Abstract
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; NS3/4A 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 12weeks. 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 300mg glecaprevir plus 120mg 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 12weeks 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.
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; NS3/4A 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 12weeks. 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 300mg glecaprevir plus 120mg 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 12weeks 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.
Authors: Sabrina A Assoumou; Shayla Nolen; Liesl Hagan; Jianing Wang; Golnaz Eftekhari Yazdi; William W Thompson; Kenneth H Mayer; Jon Puro; Lin Zhu; Joshua A Salomon; Benjamin P Linas Journal: Am J Med Date: 2020-06-27 Impact factor: 4.965
Authors: Linah N Rusere; Ashley N Matthew; Gordon J Lockbaum; Muhammad Jahangir; Alicia Newton; Christos J Petropoulos; Wei Huang; Nese Kurt Yilmaz; Celia A Schiffer; Akbar Ali Journal: ACS Med Chem Lett Date: 2018-05-17 Impact factor: 4.345