A5009573085- Hepatitis B Virus Studies
- Hepatitis C virus research
- Animal Virus Infections Studies
- Liver Disease Diagnosis and Treatment
- Influenza Virus Research Studies
- HIV/AIDS drug development and treatment
- Respiratory viral infections research
- Biochemical and Molecular Research
- Cytomegalovirus and herpesvirus research
- Virology and Viral Diseases
- Colorectal Cancer Treatments and Studies
- HIV Research and Treatment
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Hepatitis Viruses Studies and Epidemiology
- Drug-Induced Hepatotoxicity and Protection
- Pancreatic and Hepatic Oncology Research
- Enzyme function and inhibition
- Chemical Reactions and Isotopes
- Acute Lymphoblastic Leukemia research
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
- Bacterial Identification and Susceptibility Testing
- Herpesvirus Infections and Treatments
- Antibiotic Use and Resistance
GlaxoSmithKline (United States)
2017-2025
GlaxoSmithKline (India)
2024
GlaxoSmithKline (United Kingdom)
2022
New Leaders
2022
John Wiley & Sons (United States)
2022
Hudson Institute
2022
GlaxoSmithKline (China)
2018-2019
Research Triangle Park Foundation
1994-2017
North Carolina State University
1997
University of Iowa
1995
Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.
Chronic infection with hepatitis B virus (HBV) leads to an increased risk of death from cirrhosis and hepatocellular carcinoma. Functional cure rates are low current treatment options (nucleos(t)ide analogs (NAs) pegylated interferons). Bepirovirsen is antisense oligonucleotide targeting all HBV messenger RNAs; in cell culture animal models, bepirovirsen reductions HBV-derived RNAs, DNA viral proteins. This phase 2 double-blinded, randomized, placebo-controlled trial the first evaluation...
The anti-hepatitis B (anti-HBV) activities of the (-) and (+) enantiomers cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (2'-deoxy-3'-thia-5-fluorocytosine [FTC]) were studied by using an HBV-transfected cell line (HepG2 derivative 2.2.15, subclone P5A). isomer was found to be a potent inhibitor viral replication, with apparent 50% inhibitory concentration 10 nM, while considerably less active. Both isomers showed minimal toxicity HepG2 cells (50% concentration, > 200...
Abstract GSK3389404 is a liver‐targeted antisense oligonucleotide that inhibits synthesis of hepatitis B surface antigen and all other virus proteins. This first‐in‐human, randomized, double‐blind, phase 1 study assessed the safety pharmacokinetics administered subcutaneously (SC) in healthy subjects. Four single ascending‐dose cohorts (10 mg, 30 60 120 mg) 3 multiple (30 mg once weekly for 4 weeks) each comprised 6 subjects randomized to 2 placebo. There were no serious adverse events (AEs)...
Background In the B-Clear study, bepirovirsen 300 mg for 24 weeks achieved hepatitis B surface antigen (HBsAg) and virus (HBV) DNA<lower limit of quantification (LLOQ) in 9% participants on nucleos[t]ide analogues (NA). The B-Together study assessed if sequential bepirovirsen/pegylated interferon (PegIFN) therapy can improve efficacy rates.
Bepirovirsen is an antisense oligonucleotide currently in Phase 3 development to treat chronic hepatitis B virus (HBV) infection. Given the importance of coadministration bepirovirsen and standard-of-care nucleos(t)ide analogs (NAs), we evaluated drug-drug interactions (DDIs) between bepirovirsen, entecavir (ETV), tenofovir (TFV) using vitro clinical data obtained through innovative study design sampling strategy. Static models employing indicated that not a direct inhibitor or inducer most...
Objectives: Bepirovirsen, an antisense oligonucleotide that targets all hepatitis B virus (HBV) RNAs, reduced surface antigen (HBsAg) levels in Phase 2 studies participants with chronic HBV infection. Transient increases alanine aminotransferase (ALT) were often observed concurrent HBsAg reduction.[1] The objectives of this work to develop a mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model describe the effects bepirovirsen on and ALT, identify predictors response, perform...
The (-) enantiomer of cis-5-fluoro-1l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(-)-FTC)], a substituted oxathiolane compound with anti-hepatitis B virus activity in vitro, was assessed for its efficacy woodchucks naturally acquired woodchuck hepatitis (WHV) infection. Pharmacokinetics and vitro anabolism were also determined. (-)-FTC anabolized to the 5'-triphosphate dose-related fashion, reaching maximum concentration at about 24 h cultured hepatocytes. Following administration dose...
The (-) and (+) enantiomers of the nucleoside analog cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (2',3'-dideoxy-5-fluoro-3'-thiacytidine; FTC) have been shown to inhibit hepatitis B virus replication in vitro HepG2 derivative 2.2.15 (subclone P5A) cells. (-)-FTC (+)-FTC were anabolized 5'-monophosphate, 5'-diphosphate, 5'-triphosphate this cell line. was more efficiently phosphorylated than (+)-FTC, levels 3.6 0.2 pmol/10(6) cells, respectively, detected after incubation...
4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most antivirally active member of a novel class optically isomeric dideoxynucleosides in which base has been transposed from natural 1' position to 2' and absolute configuration (S,S). IsoddA was against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 ZY), HIV-1 clinical isolates. Combinations compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or...
A murine model was developed to investigate the in vivo activity of anti-hepatitis B virus (HBV) agents. Mice with subcutaneous tumors HBV-producing 2.2.15 cells showed reductions levels HBV serum and intracellular when mice were orally dosed (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC). No effects on tumor size or alpha-fetoprotein observed. FTC can selectively inhibit replication at nontoxic doses.
Dose-dependent reductions in hepatitis B virus (HBV) RNA, DNA, and viral proteins following bepirovirsen administration were observed HepG2.2.15 cells. In HBV-transgenic mice treated at 50 mg/kg/wk, hepatic HBV RNA DNA reduced by 90% 99%, respectively. Subsequently, a phase 1 first-in-human study assessed pharmacokinetics tolerability of single (75-450 mg) multiple (150-450 mg on days 1, 4, 8, 11, 15, 22) subcutaneous doses 96 healthy volunteers. Bepirovirsen all dose levels was rapidly...
Long-acting (LA) cabotegravir demonstrated superior efficacy versus daily oral standard-of-care for HIV-1 preexposure prophylaxis. This phase 1 study assessed safety, tolerability, pharmacokinetics, and acceptability of in 47 HIV-negative adult Chinese men at low risk acquiring HIV-1.