bepirovirsen (GSK3228836) / GSK, Ionis - LARVOL DELTA

Clinically meaningful rates of functional cure in virologically suppressed patients with chronic hepatitis B infection treated with bepirovirsen: B-Well phase 3 trials (EASL 2026) - No abstract available

Clinical • P3 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Up to 24 months durability of functional cure in response to bepirovirsen plus Peg-IFN sequential therapy in B-Together responders: results from the B-Sure study (EASL 2026) - No abstract available

Hepatitis B • Hepatology • Infectious Disease

Up to 36 months durability of functional cure in response to bepirovirsen therapy in B-Clear On-NA responders: results from the B-Sure study (EASL 2026) - No abstract available

Hepatitis B • Hepatology • Infectious Disease

Up to 36 months durability of functional cure in response to bepirovirsen therapy in B-Clear Not-on-NA responders: results from the B-Sure study (EASL 2026) - No abstract available

Hepatitis B • Hepatology • Infectious Disease

Functional analysis of clinically observed SNPs in the bepirovirsen binding site reveals reduced HBV fitness via impaired HBx/HBV polymerase activity in vitro (EASL 2026) - No abstract available

Preclinical • Hepatitis B

PBPK Modelling of Antisense Oligonucleotide Therapeutics: Application for Predicting Plasma and Tissue Pharmacokinetics of Bepirovirsen. (PubMed, AAPS J) - "The PBPK model predicted the liver and kidney tissue Cmax values to be 172 and 132 µg/mL, respectively. In conclusion, a PBPK modelling approach for bepirovirsen, an ASO, is presented in this article and offers opportunities for future applications to other oligonucleotide therapeutics."

First-in-human • Journal • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Bepirovirsen accepted for regulatory review in Japan as a potential first-in-class treatment for chronic hepatitis B (GSK Press Release) - "The regulatory submission is supported by positive results from the B-Well 1 and B-Well 2 Phase III trials, where bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate....The data are anticipated to be presented at a congress and submitted for scientific peer-reviewed publication in 2026."

Japan filing • P3 data • Hepatitis B

GSK PLC has announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has accepted the new drug application (NDA) for bepirovirsen, an investigational antisense oligonucleotide (ASO), for the treatment of adults with chronic hepatitis B (CHB). (Market Screener) - "This acceptance marks the first regulatory filing globally for bepirovirsen, which has been granted SENKU designation in Japan, enabling expedited review. The submission is supported by positive results from the B-Well 1 and B-Well 2 Phase III trials, demonstrating statistically significant and clinically meaningful functional cure rates."

Japan filing • Hepatitis B

Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus) (clinicaltrials.gov) - P2 | N=157 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2027 ➔ Apr 2027

Enrollment closed • Trial primary completion date • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Single nucleotide polymorphisms in the bepirovirsen binding site have limited impact on treatment response in chronic hepatitis B. (PubMed, J Hepatol) - P2b | "The majority of participants achieved >1 log HBsAg reductions, including transient HBsAg loss in some, though numerically smaller HBsAg reductions in participants with baseline SNPs require further investigation to better understand resistance mechanisms to bepirovirsen."

Journal • Hepatitis B • Infectious Disease • Inflammation

An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection. (PubMed, Nat Commun) - "Toxicity studies in Sprague-Dawley rats and cynomolgus monkeys indicate satisfactory biosafety profiles of KC13-M2G2. Given that elebsiran and bepirovirsen have achieved a functional cure rate of no more than 20% in their clinical studies, KC13-M2G2 as a more potent candidate drug is expected to exhibit superior performance in clinical applications."

Journal • Hepatitis B • Infectious Disease • Inflammation

Beyond immune activation: unresolved questions in bepirovirsen's mechanism of action toward HBV functional cure. (PubMed, Hepatol Int) - No abstract available

Journal

Comment on 'Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study)'. (PubMed, Hepatol Int) - No abstract available

Journal • Immunology

Beyond ALT flares: rethinking immune activation and mechanistic interpretation in bepirovirsen-treated chronic hepatitis B. (PubMed, Hepatol Int) - No abstract available

Journal • Hepatitis B • Infectious Disease • Inflammation

Assessment of Health State Utilities Associated With Treatment for Chronic Hepatitis B Virus (HBV) Infection (ISPOR-EU 2025) - "New treatments, such as bepirovirsen (an unconjugated antisense oligonucleotide currently in Phase 3 studies), are being developed with the goal of functional cure (i.e., long-term HBV surface antigen loss and undetectable HBV DNA after cessation of therapy)... The highest utilities were found for health states describing functional cure and the period immediately preceding functional cure (NA cessation). Health states describing treatment with Peg-IFN had the lowest utilities, possibly due to drug-associated adverse events. Information from this study may be useful in models examining cost-effectiveness of HBV treatments."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Beyond viral suppression: assessing the immunotherapeutic potential of bepirovirsen for chronic hepatitis B. (PubMed, Hepatol Int) - No abstract available

Journal • Hepatitis B • Infectious Disease • Inflammation

GSK presents data from its advancing liver pipeline at AASLD 2025 (GSK Press Release) - "21 abstracts highlight advances in the treatment of liver conditions, building from GSK’s expertise in inflammation and fibrosis; Phase II B-Sure study sub-analysis shows durability of functional cure in chronic hepatitis B (CHB) patients treated with bepirovirsen and pegylated interferon (Peg-IFN); Late breaking results for once-monthly efimosfermin in metabolic dysfunction-associated steatohepatitis (MASH), supporting the start of phase III clinical trials"

Clinical data • Hepatitis B • Metabolic Dysfunction-Associated Steatohepatitis

Comment on "Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study)". (PubMed, Hepatol Int) - No abstract available

Journal • Immunology

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 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed

Trial completion • Hepatitis B • Infectious Disease • Inflammation

A Phase 1, Randomized, Open-Label, Parallel Group Study to Evaluate the Relative Bioavailability and Safety of Subcutaneous Bepirovirsen when Delivered from a Vial or Prefilled Syringe Fitted with a Safety Syringe Device in Healthy Adult Participants. (PubMed, Clin Pharmacol Drug Dev) - P1 | "These findings confirm that PFS SSD is a viable alternative to vials for bepirovirsen administration, when HCP- or self-administered, for the treatment of chronic HBV. Clinical trial identifier: NCT06058390."

Journal • P1 data • Hepatitis B • Infectious Disease • Inflammation

RETROSPECTIVE ANALYSIS OF B-CLEAR STUDY HBSAG LEVELS WITH THE ULTRASENSITIVE LUMIPULSE HBSAG ITACT ASSAY AND ASSOCIATION WITH RESPONSE AND RELAPSE (AASLD 2025) - "Background: Bepirovirsen is an unconjugated antisense oligonucleotide in development for chronic hepatitis B virus (HBV) infection that has been shown to reduce hepatitis B surface antigen (HBsAg). The iTACT HBsAg assay provides additional data with improved resolution to support pharmacokinetic/pharmacodynamic modeling. However, further studies with larger sample sizes and additional time points are needed to confirm the findings. References: 1."

Retrospective data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A NOVEL MRNA-BASED IMMUNOTHERAPY ACHIEVES COMPLETE ELIMINATION OF HUMAN HEPATITIS B VIRUS IN CHRONIC HBV MOUSE MODELS (AASLD 2025) - " We developed two mRNA-based immunomodulators (IMs) and evaluated their therapeutic potential in combination with entecavir and either a siRNA (Elebsiran) or an ASO (Bepirovirsen) in two distinct chronic HBV mouse models for elimination of HBV both in the periphery and intrahepatic compartment. Combination therapies containing one of the IMs led to a rapid and profound decline in HBsAg and HBV DNA, whereas prophylactic HBV vaccine (Engerix) had minimum impact on these viral markers... Our study demonstrated that either novel IMs, when used in combination with direct antivirals, achieved a rapid, robust, and sustained suppression of HBV infection in chronic mouse models. We observed rapid and sustained declines in HBsAg and HBV DNA in plasma and HBcAg in the liver. Unlike treatments lacking the IMs, which only induced a rapid yet transient HBsAg and HBV DNA decline followed by a rapid rebound of these viral markers once the treatments were discontinued, our approach..."

IO biomarker • Preclinical • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

PROTEOMIC PROFILING IN PREFILLED SYRINGE STUDY DEMONSTRATES BEPIROVIRSEN'S IMMUNE STIMULATORY EFFECT (AASLD 2025) - P1, P2 | "These data demonstrate that bepirovirsen mediates a strong innate immune response, with the highest activity observed at 24–48 hours, suggesting a sustained immune response that lasts at least 48 hours. The similar immune protein profile changes observed in patients with chronic HBV infection and in healthy volunteers in this study suggests that this immune response is stimulated by bepirovirsen treatment regardless of the presence of HBV. Funding: GSK (219239)"

Hepatitis B • Hepatology • Infectious Disease • Inflammation

TRIPLE-TARGETING IMMUNOMODULATOR C3 TREATMENT PROMOTES HBV CLEARANCE THROUGH FUNCTIONAL RECONSTITUTION OF HOST IMMUNITY IN HBV-CARRIER MOUSE MODELS (AASLD 2025) - "Besides, the combinatorial antiviral efficacy and response maintenance after withdraw of bepirovirsen or siRNA (si1260/1848) with C3 was systematically evaluated in rAAV8-1.3X HBV mouse models... The triple-targeting immunomodulator C3 could eliminate HBV infection and ameliorate the viral rebound via host immune system activation, representing C3 a promising CHB therapeutic candidate."

Immunomodulating • Preclinical • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

INTRAHEPATIC AND PERIPHERAL IMMUNOPHENOTYPING OF PARTICIPANTS WITH CHRONIC HEPATITIS B RECEIVING BEPIROVIRSEN IN THE B-FINE STUDY STRONGLY SUGGESTS THAT BEPIROVIRSEN MAY TRIGGER A HUMORAL RESPONSE (AASLD 2025) - P2 | "The proteomic, transcriptomic (liver and peripheral) and flow cytometry data obtained from the B-Fine study strongly suggest that bepirovirsen triggers a humoral immune response in treated pts. Three pts achieved HBsAg loss following bepirovirsen treatment. Funding: GSK (212602)"

Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD20 • CD22 • CD80 • CXCR6 • FCRLB • MS4A1