elebsiran (VIR-2218) / Alnylam, Vir Biotech, Brii Biosci - LARVOL DELTA

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

A Platform Study to Evaluate Investigational Therapies in Chronic Hepatitis B Infection (clinicaltrials.gov) - P1/2 | N=33 | Completed | Sponsor: Vir Biotechnology, Inc. | Active, not recruiting ➔ Completed | N=150 ➔ 33 | Trial completion date: Mar 2027 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Hepatitis B • Infectious Disease • Inflammation

SOLSTICE: tobevibart plus elebsiran for hepatitis D. (PubMed, Nat Rev Gastroenterol Hepatol) - No abstract available

Journal • Inflammation

A Study to Evaluate Tobevibart + Elebsiran in Chronic HDV Infection (clinicaltrials.gov) - P3 | N=124 | Active, not recruiting | Sponsor: Vir Biotechnology, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Inflammation

A Phase 2 Trial of Tobevibart plus Elebsiran in Hepatitis D. (PubMed, N Engl J Med) - P2 | "In this phase 2 trial, tobevibart plus elebsiran as well as tobevibart monotherapy decreased HDV RNA and ALT levels through week 48. Treatment with tobevibart plus elebsiran was associated with a high incidence of undetectable HDV RNA and of a decrease in the HBsAg level. (Funded by Vir Biotechnology; ClinicalTrials.gov number, NCT05461170.)."

Journal • P2 data • Hepatitis B • Infectious Disease • Inflammation • Influenza • Respiratory Diseases

Elebsiran and PEG-IFNα for chronic hepatitis B infection: a partially randomized, open-label, phase 2 trial. (PubMed, Nat Med) - P2 | "Functional cure is a goal for the treatment of chronic hepatitis B virus (HBV) infection; however, it is infrequently achieved with currently approved treatments. Furthermore, the increased HBsAg loss rate in BRII-179 anti-HBs responders suggests that BRII-179 may be a valuable tool for immunological profiling to optimize curative outcomes in patients with HBV infection. ClinicalTrials.gov registration: NCT05970289 ."

Journal • P2 data • Hepatitis B • Infectious Disease • Inflammation • IFNA1

MARCH: Study of VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection (clinicaltrials.gov) - P2 | N=244 | Active, not recruiting | Sponsor: Vir Biotechnology, Inc. | Trial completion date: Jun 2027 ➔ Mar 2026 | Trial primary completion date: Jun 2027 ➔ Mar 2026

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

ECLIPSE: A PIVOTAL PROGRAM EVALUATING ONCE-MONTHLY COMBINATION THERAPY WITH TOBEVIBART AND ELEBSIRAN FOR CHRONIC HDV INFECTION - RATIONALE, STUDY DESIGN, AND OBJECTIVES (AASLD 2025) - "ECLIPSE 2 compares tobevibart+elebsiran vs bulevirtide (BLV) monotherapy in participants who have not achieved HDV RNA TND on BLV. Tobevibart+elebsiran combination therapy has the potential to address a significant unmet need in chronic HDV infection, including in participants who do not have an approved treatment and those who did not achieve HDV RNA TND on BLV monotherapy."

Combination therapy • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

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

HBSAG DECLINES OBSERVED WITH VRON-0200 ALONE ARE RAPIDLY ENHANCED WITH THE ADDITION OF COMBINATION ANTIVIRAL THERAPIES: RESULTS: FROM A PHASE 1B STUDY FOR FUNCTIONAL CURE IN CHRONICALLY HBV-INFECTED PATIENTS (AASLD 2025) - "VRON-0200 alone, or in combination, had no observed safety concerns, and was well tolerated. Despite not targeting HBsAg, a single VRON-0200 dose was able to lower S-antigen in ~25% of pts. The combination of VRON-0200 with elebsiran and tobevibart rapidly and profoundly enhanced VRON-0200 HBsAg declines within 7 days in all pts, with further declines being observed with additional doses."

Clinical • P1 data • Hepatitis B • CD8 • IFNG

EFFECT OF TOBEVIBART (VIR-3434) AND ELEBSIRAN (VIR-2218) MONOTHERAPY ON HEPATITIS B SURFACE ANTIGEN COMPOSITION IN PATIENTS WITH CHRONIC HEPATITIS B (AASLD 2025) - "Tobevibart led to significant reductions in LHBs and MHBs levels, and MHBs proportions in patients with BL HBsAg <3000 IU/mL. Elebsiran, in contrast, effectively suppressed LHBs and MHBs with sustained undetectable MHBs regardless of HBsAg baseline levels. Our findings suggest differential effects of the two agents on cccDNA-related HBsAg expression and support further evaluation of LHBs and MHBs as predictors of functional cure."

Clinical • Monotherapy • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

EFFICACY AND SAFETY OF TOBEVIBART (VIR-3434) ALONE OR IN COMBINATION WITH ELEBSIRAN (VIR-2218) IN PARTICIPANTS WITH CHRONIC HEPATITIS DELTA VIRUS INFECTION: WEEK 48 ENDPOINT RESULTS: FROM THE PHASE 2 SOLSTICE TRIAL (AASLD 2025) - P2 | "At 48 weeks of therapy, higher rates of antiviral responses including HDV RNA TND and reductions in HBsAg were observed in participants receiving tobevibart+elebsiran Q4W; whereas lower antiviral rates were observed in participants receiving tobevibart Q2W. Adverse events were generally mild to moderate and transient, with no treatment-related SAEs observed. These results support further development of tobevibart+elebsiran Q4W, which is now being evaluated in a comprehensive registrational phase 3 ECLIPSE program in participants with chronic HDV infection."

Clinical • Combination therapy • P2 data • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation • Influenza • Musculoskeletal Pain • Respiratory Diseases

A Study to Evaluate Tobevibart+Elebsiran Versus Bulevirtide in Chronic HDV Infection (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Vir Biotechnology, Inc.

New P2 trial • Infectious Disease • Inflammation

SOLSTICE: Combination Therapy for the Treatment of Chronic Hepatitis D Infection. (clinicaltrials.gov) - P2 | N=95 | Active, not recruiting | Sponsor: Vir Biotechnology, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Inflammation

A Study to Evaluate Tobevibart+Elebsiran in Participants With Chronic HDV Infection Not Virologically Suppressed With Bulevirtide (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Vir Biotechnology, Inc.

New P3 trial • Infectious Disease • Inflammation

Hope on the horizon: Emerging therapies for hepatitis D. (PubMed, World J Hepatol) - "Pegylated interferon lambda acts on interferon-lambda (Type III) receptors predominantly expressed in hepatocytes. In 2023, bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D. This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells, which is the primary entry point for the virus...Two more viral entry inhibitors are HH003 and tobevibart. Other agents include nucleic acid polymers (REP 2139-Mg), prenylation inhibitors (lonafarnib), and RNA interference-based therapies (elebsiran)...The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1, 2, and 3 trials. With these new treatments on the horizon, the prospects for improved HDV patient outcomes are promising."

Journal • Review • Hepatitis B • Infectious Disease • Inflammation • IFNA1

Advances in treatment of hepatitis delta virus infection: Update on novel investigational drugs. (PubMed, World J Virol) - "Significant unmet medical needs remain in the treatment of HDV, and recent advances in drug development offer hope for meaningful advances in drug therapy which may improve virologic response rates and clinical outcomes. This review summarizes trial design and available efficacy data from key phase 2 and 3 trials for investigational therapies including entry inhibitors (bulevirtide), prenylation inhibitors (lonafarnib), novel IFNs (peginterferon lambda), RNA interference molecules (JNJ-3989, elebsiran), monoclonal antibodies (tobevibart), and nucleic acid polymers (REP2139), and addresses future directions in HDV pharmacotherapy."

Journal • Review • Fibrosis • Gastroenterology • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor

A Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics and Safety of VIR-2218 (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Vir Biotechnology, Inc. | Active, not recruiting ➔ Completed

Trial completion • Renal Disease

Therapy with murinized tobevibart and elebsiran is efficacious in a liver-chimeric mouse model of HDV infection. (PubMed, JHEP Rep) - "Tobevibart and elebsiran are currently being evaluated in clinical trials for the treatment of HDV (phase III) and for the treatment of HBV (phase II). The current study demonstrates that tobevibart and elebsiran are efficacious in preclinical models of HBV/HDV coinfection, supporting their clinical development."

Journal • Preclinical • Hepatitis B • Hepatocellular Cancer • Infectious Disease • Inflammation • Oncology • Solid Tumor

Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Virion Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2025 ➔ Mar 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial primary completion date • Hepatitis B • Infectious Disease • Inflammation

A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE) (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Brii Biosciences Limited | N=180 ➔ 250 | Active, not recruiting ➔ Recruiting

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

A Study to Evaluate Tobevibart+Elebsiran in Chronic Hepatitis Delta Virus (HDV) Infection (ECLIPSE 1) (ANZCTR) - P3 | N=120 | Not yet recruiting | Sponsor: Vir Biotechnology, Inc.

New P3 trial • Infectious Disease • Inflammation

Brii Bio Presents Late-Breaking Data from Its Ongoing Phase 2 ENSURE Study at EASL Congress 2025, Suggesting BRII-179's Role in Advancing Higher HBsAg Loss (PRNewswire) - P2 | N=75 | ENSURE (NCT05970289) | Sponsor: Brii Biosciences Limited | "18 and 10 participants had peak anti-HBs titer ≥ 10 IU/L (defined as anti-HBs responders) and < 10 IU/L (defined as non-responders) induced by BRII-179 in the previous study, respectively...Among the anti-HBs responders who lost HBsAg, 91% (10/11) had anti-HBs titers ≥ 100 IU/L at EOT; BRII-179 experienced participants achieved HBsAg loss faster than BRII-179 naïve participants, with 83% (10/12) of HBsAg loss occurring by Week 24 (vs 55% [6/11] in BRII-179 naïve participants); Elebsiran + PEG-IFNα was generally safe and tolerated in BRII-179 experienced participants...Incidence of treatment emergent adverse events (TEAEs) was comparable between combination therapy cohorts and PEG-IFNα alone cohort. Most TEAEs were consistent with known side effects of PEG-IFNα....Key data readouts will be shared in the coming months at scientific conferences throughout 2025."

Late-breaking abstract • P2 data • Hepatitis B

Rapid HBsAg declines and HBsAb seroconversion observed with a single dose of VRON-0200 plus Tobevibart and Elebsiran: preliminary results of a VRON-0200 combination treatment from a phase 1b study for functional cure in chronically HBV-infected patients (EASL 2025) - "These initial data of the combination of a single i.m. VRON-0200 dose plus Tobevibart and Elebsiran had no observed safety concerns, was well tolerated, and displayed rapid (within 7 days of the addition of Tobevibart and Elebsiran) HBsAg declines and HBsAb seroconversions in all 4 (100%) patients. These initial responses appear promising, compared to investigational combin- ation regimens, reported to date, including those containing PEG-IFN. These data, coupled with VRON-0200's safety, tolerability and ease of administration, may eventually support its use as an IFN-sparing immunotherapy, with the potential for shorter duration combination treatments for HBV functional cure."

Clinical • Late-breaking abstract • P1 data • Hepatitis B • CD8

Chronic hepatitis B virus infected participants responding to prior BRII-179 treatment achieved faster and higher rate of hepatitis B virus surface antigen seroclearance on elebsiran plus peginterferon-alfa: end of treatment data from ENSURE study (EASL 2025) - P2 | "After receiving elebsiran plus PEG-IFN alfa treatment, a substantially higher rate of HBsAg seroclearance was achieved in participants who had BRII-179 induced anti-HBs response (respon- ders) than in those who did not (non-responders). These responders also achieved faster HBsAg seroclearance compared to those without prior BRII-179 treatment, most of whom achieved HBsAg seroclear- ance after 24 weeks of elebsiran + PEG-IFN alfa (Jia, 2024; Yuen, 2022). These data suggest that BRII-179 induced immune responses may identify patients who are more responsive to curative treat- ments."

Late-breaking abstract • Hepatitis B • Hepatology • Idiopathic Arthritis • Infectious Disease • Inflammation • IFNA1