Ledipasvir Plus Sofosbuvir for 12 Weeks in Patients With Hepatitis C Genotype 4 Infection.
|Title||Ledipasvir Plus Sofosbuvir for 12 Weeks in Patients With Hepatitis C Genotype 4 Infection.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Abergel, A., S. Metivier, D. Samuel, D. Jiang, K. Kersey, P. S. Pang, E. Svarovskaia, S. J. Knox, V. Loustaud-Ratti, and T. Asselah|
|Journal||Hepatology (Baltimore, Md.)|
|Date Published||2016 Jun 28|
Genotype 4 hepatitis C virus (HCV) was considered difficult to treat in the era of peginterferon-alfa and ribavirin regimens. We evaluated the efficacy and safety of therapy with the NS5A 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 ledipasvir and 400 mg 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% (41/44; 95% CI, 81% to 99%). SVR12 rates were similar between treatment-naïve (95%, 21/22) and treatment-experienced (91%, 20/22) 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.
CONCLUSIONS: 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) This article is protected by copyright. All rights reserved.