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Abstract Details
Safety and efficacy of vebicorvir administered with entecavir in treatment-naïve patients with chronic hepatitis B virus infection
J Hepatol. 2022 Jun 10;S0168-8278(22)00348-8. doi: 10.1016/j.jhep.2022.05.027.Online ahead of print.
1Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: msulkowski@jhmi.edu.
2Institute of Liver Studies, King's College Hospital, London, UK.
3Office of Xiaoli Ma, Philadelphia, PA, USA.
4T Nguyen Research and Education, Inc., San Diego, CA, USA.
5Schiff Center for Liver Diseases, University of Miami School of Medicine, Miami, FL, USA.
6Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
7Department of Medicine, Division of Liver Diseases, Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA.
8ID Care, Hillsborough, NJ, USA.
9NYU Langone Health, New York, NY, USA.
10Sing Chan MD, New York, NY, USA.
11Pfleger Liver Institute, University of California, Los Angeles, CA, USA.
12New Zealand Clinical Studies, Auckland, New Zealand.
13Medical Associates Research Group, San Diego, CA, USA.
14Assembly Biosciences, South San Francisco, CA, USA.
15Quest Clinical Research, San Francisco, CA, USA.
16Cedars-Sinai Medical Center, Los Angeles, CA, USA.
17Waikato Hospital, Hamilton, New Zealand.
18Gastrohealth, Catonsville, MD, USA.
19GastroIntestinal Research Institute, Vancouver, Canada.
20Stanford University Medical Center, Stanford, CA, USA.
21Toronto Liver Centre, Toronto, Canada.
22Southern California Research Center, Coronado, CA, USA.
23Asian Pacific Liver Center, Los Angeles, CA, USA.
24University of Toronto, Toronto, Canada.
25Department of Medicine and State Key Laboratory of Liver Research, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Abstract
Background and aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress hepatitis B virus (HBV) DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor which interferes with multiple aspects of HBV replication. This phase 2 trial (NCT03577171) evaluated the efficacy and safety of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV.
Methods: Hepatitis B "e" antigen positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner, to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV for 24 weeks (W). The primary endpoint was change in mean log10 HBV DNA from Baseline to W12 and W24.
Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At W12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log10 IU/mL HBV DNA (-4.45 [1.03]) vs PBO+ETV (-3.30 [1.18]; p=0.0077). At W24, VBR+ETV led to a greater reduction from Baseline in log10 IU/mL HBV DNA (-5.33 [1.59]) vs PBO+ETV (-4.20 [0.98]; p=0.0084). Greater mean reductions in pregenomic RNA were observed at W12 and W24 in patients receiving VBR+ETV vs PBO+ETV (p<0.0001 and p<0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. Safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious AEs, or evidence of drug-induced liver injury.
Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV with a favourable safety and tolerability profile.
Lay summary: Hepatitis B is a long-lasting viral infection of the liver. This study demonstrates that vebicorvir (a core inhibitor) with entecavir is generally safe, well tolerated, and demonstrates greater antiviral activity compared with entecavir alone in treatment-naïve patients chronically infected with hepatitis B virus. This study supports continued evaluation of vebicorvir in the treatment of chronic hepatitis B.