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Efficacy and safety of vebicorvir administered in virologically-suppressed patients with chronic hepatitis B virus infection. Journal of hepatology Yuen, M. F., Agarwal, K., Ma, X., Nguyen, T. T., Schiff, E. R., Hann, H. L., Dieterich, D. T., Nahass, R. G., Park, J. S., Chan, S., Han, S. B., Gane, E. J., Bennett, M., Alves, K., Evanchik, M., Yan, R., Huang, Q., Lopatin, U., Colonno, R., Ma, J., Knox, S. J., Stamm, L. M., Bonacini, M., Jacobson, I. M., Ayoub, W. S., Weilert, F., Ravendhran, N., Ramji, A., Kwo, P. Y., Elkhashab, M., Hassanein, T., Bae, H. S., Lalezari, J. P., Fung, S. K., Sulkowski, M. S. 2022

Abstract

Hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitors (NrtI) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase 2 trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically-suppressed patients on NrtI.Noncirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B "e" antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks.Of 73 patients enrolled, 47 and 26 were HBeAg?positive and negative. In HBeAg positive and negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline receiving VBR+NrtI achieved DNA target not detected at Week 24 compared to PBO+NrtI. In HBeAg?positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported.In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was evident by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone.Core inhibitors represent a novel approach to treating chronic HBV infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.NCT03576066.

View details for DOI 10.1016/j.jhep.2022.04.005

View details for PubMedID 35460726