Armand Abergel1, Sophie Metivier2, Didier Samuel3, Deyuan Jiang4, Kathryn Kersey4, Phillip S Pang4, Evguenia Svarovskaia4, Steven J Knox4, Veronique Loustaud-Ratti5, Tarik Asselah6. 1. Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Estaing, Université d'Auvergne, UMR CNRS 6284, Clermont-Ferrand, France. aabergel@chu-clermontferrand.fr. 2. Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Purpan, Toulouse, France. 3. Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, UMR-S 1193, Université Paris-Sud, INSERM U785, Villejuif, France. 4. Gilead Sciences, Inc, Foster City, CA. 5. Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Limoges, U850 INSERM, Université de Limoges, Limoges, France. 6. Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot and INSERM UMR1149, Clichy, France.
Abstract
UNLABELLED: Genotype 4 hepatitis C virus (HCV) was considered difficult to treat in the era of pegylated interferon-alpha (Peg-IFN-α) and ribavirin regimens. We evaluated the efficacy and safety of therapy with the nonstructural (NS) 5A inhibitor, ledipasvir, combined with the NS5B polymerase inhibitor, sofosbuvir, in patients with HCV genotype 4. In this phase 2, open-label study, 44 patients (22 treatment naïve and 22 treatment experienced) received a fixed-dose combination tablet of 90 mg of ledipasvir and 400 mg of sofosbuvir orally once-daily for 12 weeks. The primary endpoint was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (SVR12). Among study participants, HCV genotype 4 subtypes were well represented (4a, n = 25; 4d, n = 10; other subtypes, n = 9). Ten patients (23%) had compensated cirrhosis. Of the 22 treatment-experienced patients, 21 (95%) had a non-CC IL-28B genotype. All 44 patients completed the full 12 weeks of dosing. The SVR12 rate was 93% (41 of 44; 95% confidence interval, 81-99). SVR12 rates were similar between treatment-naïve (95%; 21 of 22) and treatment-experienced (91%; 20 of 22) patients. All 3 patients who did not achieve SVR12 had virological relapse within 4 weeks of the end of treatment; all 3 had baseline HCV RNA ≥800,000 IU/mL, a non-CC IL-28B genotype, and pretreatment NS5A resistance-associated variants. None of the patients who relapsed had cirrhosis. The most common adverse events were asthenia, headache, and fatigue. No patients experienced a serious adverse event. CONCLUSION: The all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV 4 subtypes in both treatment-naïve and -experienced patients, including those with compensated cirrhosis. (EudraCT number: 2013-003978-27; Clinicaltrials.gov NCT02081079) (Hepatology 2016;64:1049-1056).
UNLABELLED: Genotype 4 hepatitis C virus (HCV) was considered difficult to treat in the era of pegylated interferon-alpha (Peg-IFN-α) and ribavirin regimens. We evaluated the efficacy and safety of therapy with the nonstructural (NS) 5A inhibitor, ledipasvir, combined with the NS5B polymerase inhibitor, sofosbuvir, in patients with HCV genotype 4. In this phase 2, open-label study, 44 patients (22 treatment naïve and 22 treatment experienced) received a fixed-dose combination tablet of 90 mg of ledipasvir and 400 mg of sofosbuvir orally once-daily for 12 weeks. The primary endpoint was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (SVR12). Among study participants, HCV genotype 4 subtypes were well represented (4a, n = 25; 4d, n = 10; other subtypes, n = 9). Ten patients (23%) had compensated cirrhosis. Of the 22 treatment-experienced patients, 21 (95%) had a non-CC IL-28B genotype. All 44 patients completed the full 12 weeks of dosing. The SVR12 rate was 93% (41 of 44; 95% confidence interval, 81-99). SVR12 rates were similar between treatment-naïve (95%; 21 of 22) and treatment-experienced (91%; 20 of 22) patients. All 3 patients who did not achieve SVR12 had virological relapse within 4 weeks of the end of treatment; all 3 had baseline HCV RNA ≥800,000 IU/mL, a non-CC IL-28B genotype, and pretreatment NS5A resistance-associated variants. None of the patients who relapsed had cirrhosis. The most common adverse events were asthenia, headache, and fatigue. No patients experienced a serious adverse event. CONCLUSION: The all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV 4 subtypes in both treatment-naïve and -experienced patients, including those with compensated cirrhosis. (EudraCT number: 2013-003978-27; Clinicaltrials.gov NCT02081079) (Hepatology 2016;64:1049-1056).
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