Massimo Puoti1, Graham R Foster2, Stanley Wang3, David Mutimer4, Edward Gane5, Christophe Moreno6, Ting Tsung Chang7, Samuel S Lee8, Rui Marinho9, Jean-Francois Dufour10, Stanislas Pol11, Christophe Hezode12, Stuart C Gordon13, Simone I Strasser14, Paul J Thuluvath15, Zhenzhen Zhang3, Sandra Lovell3, Tami Pilot-Matias3, Federico J Mensa3. 1. AO Ospedale Niguarda Ca Granda, Milan, Italy. Electronic address: massimo.puoti@fastwebnet.it. 2. Queen Mary University of London, Barts Health, London, UK. 3. AbbVie Inc., North Chicago, IL, USA. 4. Queen Elizabeth Hospital and NIHR Liver Biomedical Research Unit, Birmingham, UK. 5. University of Auckland, Auckland, New Zealand. 6. CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 7. National Cheng Kung University Hospital, Tainan City, Taiwan. 8. University of Calgary, Calgary, AB, Canada. 9. Hospital S. Maria, Medical School of Lisbon, University of Lisbon, Portugal. 10. Hepatology, University Clinic for Visceral Surgery and Medicine, Bern University Hospital, Switzerland. 11. Université Paris Descartes and Hôpital Cochin, Paris, France. 12. Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France. 13. Henry Ford Health System, Detroit, MI, USA. 14. Royal Prince Alfred Hospital, Sydney, Australia. 15. Mercy Medical Center and University of Maryland School of Medicine, Baltimore, MD, USA.
Abstract
BACKGROUND & AIMS:Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed. METHODS: Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1-6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate. RESULTS: The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare. CONCLUSIONS: G/P therapy for eight weeks in patients with chronic HCV GT 1-6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks. LAY SUMMARY: In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1-6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.
RCT Entities:
BACKGROUND & AIMS:Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed. METHODS: Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1-6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate. RESULTS: The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare. CONCLUSIONS: G/P therapy for eight weeks in patients with chronic HCV GT 1-6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks. LAY SUMMARY: In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1-6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.
Authors: R Rodia; P E Meloni; V Ruggiero; S Mariotti; C Mascia; C Balestrieri; G Serra; M Conti; M Loi; F Pes; S Onali; A Perra; R Littera; F Velluzzi; L Chessa; F Boi Journal: J Endocrinol Invest Date: 2022-09-01 Impact factor: 5.467
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