bepirovirsen (GSK3228836) / GSK, Ionis - LARVOL DELTA

Study of GSK3965193 in Healthy Participants and Participants Living With Chronic Hepatitis B Infection (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: GlaxoSmithKline | Phase classification: P2 ➔ P1/2 | N=132 ➔ 84 | Trial completion date: Oct 2027 ➔ Jan 2027 | Trial primary completion date: Oct 2027 ➔ Jan 2027

Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Up to 18 months' functional cure in response to bepirovirsen therapy in B-Clear On-NA responders: B-Sure third report (EASL 2025) - No abstract available

Hepatitis B • Hepatology • Infectious Disease

Up to 2 years' functional cure in response to bepirovirsen therapy in B-Clear Not-on-NA responders: B-Sure third report (EASL 2025) - P2, P2b | "These data provide evidence of longer durability of FC observed with bepirovirsen."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Up to 18 months' functional cure in response to bepirovirsen therapy in B-Clear On-NA responders: B-Sure third report (EASL 2025) - P2 | "These data provide evidence of longer durability of FC observed with BPV."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Safety and pharmacokinetics of bepirovirsen, delivered subcutaneously by vial, or prefilled syringe fitted with a safety syringe device in healthy adult participants, and syringe device ease of use: a randomised phase 1 trial (EASL 2025) - "Participants were able to self-administer bepirovirsen using the PFS SSD, and it had a similar safety profile whether administered by an HCP or a participant, with no new safety concerns identified for bepirovirsen. The use of PFS SSD is a viable alternative for bepirovirsen administration in patients. The PK of bepirovirsen was similar across all treatment groups."

Clinical • P1 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B (EASL 2025) - No abstract available

Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study on the Safety, Efficacy and Immune Response Following Sequential Treatment With an Anti-sense Oligonucleotide Against Chronic Hepatitis B (CHB) and Chronic Hepatitis B Targeted Immunotherapy (CHB-TI) in CHB Patients Receiving Nucleos(t)Ide Analogue (NA) Therapy (clinicaltrials.gov) - P2 | N=174 | Active, not recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Feb 2026 ➔ Jun 2025 | Trial primary completion date: Feb 2026 ➔ Jun 2025

Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Durability of Response in Chinese Responders from the Global Phase 2b Study of Bepirovirsen in Participants With Chronic Hepatitis B (APASL 2025) - P2, P2b | "This interim analysis of the B-Sure study provides evidence of durability of functional cure by bepirovirsen in a subset of Chinese participants with chronic HBV infection especially in those with CR. The study is ongoing for recruitment and follow-up. Funding: GSK sponsored study 206882"

Clinical • P2b data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Characterisation of the Relationship Between HBsAg Loss and ALT Elevation During Bepirovirsen Treatment in Patients With Chronic Hepatitis B (APASL 2025) - "HBsAg reductions during bepirovirsen treatment can be achieved with or without ALT elevations. The majority of participants in both studies who experienced an ALT elevation of ≥10-fold from baseline experienced HBsAg loss. Funding: GSK (209668/209348)"

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Failure

Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Sep 2024 ➔ Apr 2025

Enrollment open • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. (PubMed, Clin Pharmacol Drug Dev) - P2, P2b | "Given the importance of coadministration of bepirovirsen and standard-of-care nucleos(t)ide analogs (NAs), we evaluated drug-drug interactions (DDIs) between bepirovirsen, entecavir (ETV), and tenofovir (TFV) using in vitro and clinical data obtained through innovative study design and sampling strategy. This analysis demonstrated no DDI potential between bepirovirsen and NAs, suggesting that dedicated clinical DDI studies are not required. Bepirovirsen is currently being evaluated in Phase 3 studies in combination with NA."

Journal • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

B-UNITED: A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB) (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study of GSK3965193 in Healthy Participants and Participants Living With Chronic Hepatitis B Infection (clinicaltrials.gov) - P2 | N=132 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Jan 2026 ➔ Oct 2027 | Trial primary completion date: Jan 2026 ➔ Oct 2027

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

SEMI-MECHANISTIC PK/PD MODELING AND SIMULATION OF SEQUENTIAL SIRNA AND BEPIROVIRSEN TREATMENT PREDICTS ADDED BENEFIT IN HBSAG RESPONSE IN SUPPORT OF PHASE 2B DOSE SELECTION (AASLD 2024) - "Funding GSK (218309) Background: Daplusiran/ tomligisiran (DAP/TOM, formerly JNJ-3989) is a fixed combination siRNA that has shown marked declines in HBsAg irrespective of baseline HBsAg but is unlikely to achieve functional cure (FC) alone. The PK-HBsAg model-based simulation results predict an added benefit of sequential DAP/TOM followed by bepirovirsen therapy versus bepirovirsen plus SOC alone due to lowering HBsAg levels with siRNA before starting bepirovirsen treatment. These results support the evaluation of this sequential regimen in a Phase 2b study."

P2b data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease

Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

COMPLETE DETERMINATION OF HEPATITIS B VIRUS GENOTYPE IN ALL PARTICIPANTS WITH CHRONIC HBV INFECTION RECEIVING NUCLEOS(T)IDE ANALOG THERAPY USING MULTI-METHOD ANALYSIS TO BETTER UNDERSTAND CLINICAL OUTCOMES: PHASE 2B B-CLEAR STUDY (AASLD 2024) - P2b | "The Phase 2b B-Clear study (NCT04449029) assessed the efficacy and safety of 12 and 24 weeks of 150–300 mg bepirovirsen treatment in pts with chronic HBV infection on or not on nucleos(t)ide analog (NA) therapy... The addition of the immunoassay method to the workflow successfully determined HBV GT in all virally suppressed B-Clear pts on NA. HBsAg reductions were observed across all major GTs. This new analysis of GT in virally suppressed pts allows for a comprehensive assessment of the association between GT, disease heterogeneity and treatment response in trials for novel HBV therapies."

Clinical • Clinical data • P2b data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure) (clinicaltrials.gov) - P2 | N=450 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Oct 2029 ➔ Feb 2029 | Trial primary completion date: Oct 2029 ➔ Feb 2029

Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Phase 1, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Bepirovirsen in Adults with Hepatic Impairment and Healthy Participants (B-Assured). (PubMed, Clin Pharmacol Drug Dev) - P1 | "Adverse events were mild. Moderate HI did not have a clinically relevant impact on bepirovirsen PK or safety."

Journal • P1 data • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B. (PubMed, J Hepatol) - P2 | "Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable and effective in participants with chronic HBV infection on stable NA. This proof-of-concept trial demonstrates a potential strategy to extend responses to bepirovirsen by reducing relapse."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study to Evaluate the Relative Bioavailability of Subcutaneous Bepirovirsen When Delivered From a Vial or Prefilled Syringe Fitted With a Safety Syringe Device in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=160 | Completed | Sponsor: GlaxoSmithKline | Recruiting ➔ Completed

Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation

B-UNITED: A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB) (clinicaltrials.gov) - P2 | N=280 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 2) (clinicaltrials.gov) - P3 | N=859 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Nonclinical phenotypic evaluation of clinically identified baseline and treatment-emergent hepatitis B Virus variants that contain single nucleotide polymorphisms in the bepirovirsen binding site (EASL-ILC 2024) - P2b | "Clinically identified baseline (BL) HBV variants were previously evaluated nonclinically for their susceptibility to the GalNAc-conjugated form of BPV, GSK3389404, in primary human hepatocytes (PHH) and to BPV in the case of HBV variant C9A using the RNA Launch model. Using our two-step system of HepG2 and PHH, we evaluated the susceptibility of clinically identified HBV BL and TE variants containing SNPs in the BPV site to BPV. The biological basis for varying levels of fitness of each variant, through potential impact of SNPs on HBx and HBV DNA polymerase function, is under evaluation. While the frequency of these HBV variants is very low, the relevance of the in vitro phenotypic data to clinical outcome is subject to further investigation."

Clinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Bepirovirsen immune mechanism of action may potentiate infected hepatocyte killing: indirect evidence from B-together peripheral longitudinal biomarker analysis (EASL-ILC 2024) - P2 | "BPV led to activation of the immune response in treated pts, providing support for an immune MoA. Three observations provide indirect evidence of a role for BPV in infected hepatocyte death: 1) presence of proliferating, activated adaptive immune cells in all response subgroups before rise in ALT; 2) increases in several liver and apoptosis-specific proteins in the serum concomitant with ALT elevations; 3) intermittent increase in HBV DNA during ALT elevations occurring more frequently in BPV responders than non-responders. Work is ongoing to further elucidate the multiple MoA of BPV and their roles in HBV functional cure."

Biomarker • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD8