tobevibart (VIR-3434) / Vir Biotech, Brii Biosci - LARVOL DELTA

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

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

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

Engineered monoclonal antibody tobevibart enhances HBsAg capture by Fc receptor-positive cells and activates HBV-specific T cells. (PubMed, J Hepatol) - P1 | "We demonstrate that tobevibart combines the advantages of potent neutralization of HBV and HDV with FcγR-mediated reduction of HBsAg and enhancement of T cell responses. Tobevibart is under clinical investigation alone or in combination with other agents to treat patients with chronic hepatitis delta and to induce functional cure of patients with CHB."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Oncology • CD4

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

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 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

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

Outcomes of 48 weeks of therapy and subsequent 24-week post-treatment period with tobevibart (VIR-3434) and elebsiran (VIR-2218) with or without pegylated interferon alfa-2a in chronic hepatitis B virus infection. Findings from the MARCH study (EASL 2025) - "The combination tobevibart and elebsiran, with or without the addition of IFN, can achieve HBsAg loss, especially in participants presenting with lower baseline HBsAg. TEAEs were predominantly mild to moderate, and no new safety concerns emerged. These positive outcomes and the overall risk-benefit profile are supportive of the further clinical development in treating chronic HBV infection."

Hematological Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Leukopenia

SOLSTICE week 24 subgroup analysis: impact of baseline viral parameters and cirrhosis status on virological and biochemical responses in participants with chronic hepatitis delta virus infection treated with tobevibart and elebsiran (EASL 2025) - No abstract available

Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation

SOLSTICE week 24 subgroup analysis: impact of baseline viral parameters and cirrhosis status on virological and biochemical responses in participants with chronic hepatitis delta virus infection treated with tobevibart and elebsiran (EASL 2025) - P2 | "In preliminary 24 weeks data, participants receiving tobevibart+elebsiran Q4W de novo therapy achieved high rates of viral suppression, regardless of baseline viral parameters or the presence of compensated cirrhosis, whereas participants receiving tobevibart Q2W with high baseline HDV viremia showed a trend towards decreased viral response. These results support continued development of tobevibart in combination with elebsiran for chronic HDV infection."

Fibrosis • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Influenza • Musculoskeletal Pain • Pain • Respiratory Diseases

A Platform Study to Evaluate Investigational Therapies in Chronic Hepatitis B Infection (clinicaltrials.gov) - P1/2 | N=150 | Active, not recruiting | Sponsor: Vir Biotechnology, Inc. | Phase classification: P2 ➔ P1/2

Phase classification • Hepatitis B • Hepatology • Infectious Disease • Inflammation

A Study to Evaluate Tobevibart + Elebsiran in Chronic HDV Infection (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Vir Biotechnology, Inc.

New P3 trial • Hepatology • Infectious Disease • Inflammation

Vir Biotechnology Enrolls First Patient in Phase 3 ECLIPSE Registrational Program for Chronic Hepatitis Delta (Businesswire) - "Vir Biotechnology, Inc...today announced the enrollment of the first patient in its Phase 3 ECLIPSE registrational program. The ECLIPSE registrational program is designed to evaluate the efficacy and safety of tobevibart in combination with elebsiran in people living with chronic hepatitis delta (CHD)."

Enrollment open • Hepatitis B