Hepcludex (bulevirtide) / Hepatera, Gilead - LARVOL DELTA

BUL-STOP: Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Hannover Medical School | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Hepatology • Infectious Disease • Inflammation

Clinical Trials for Hepatitis Delta Virus in the WHO African region: A neglected virus among neglected viruses. (PubMed, J Infect) - "HDV-focused CT are needed in the WHO African region, as the region with the highest disease burden, and unique genotypes (5-8); to evaluate efficacy of novel anti-HDV compounds and to ensure that new treatments can be distributed and deployed as they become available."

Journal • Review • Inflammation

Gilead to Present Latest Advancements Across Primary Biliary Cholangitis and Viral Hepatitis (Businesswire) - "New data to be presented at EASL will include a subgroup analysis from ASSURE, an ongoing open-label study, and an analysis of the Phase 3 RESPONSE trial and the open-label extension. Data will reinforce the effectiveness of Livdelzi (seladelpar), known as Lyvdelzi in the European Union, in reducing pruritus (chronic itch), a debilitating common symptom of primary biliary cholangitis (PBC). Moreover, the results will highlight seladelpar’s ability to deliver a sustained biochemical response regardless of prior treatment history, and as an option for a broad range of people with PBC....Key findings from 29 accepted abstracts will include two oral presentations showcasing new data on the critical goal of maintained virologic response following treatment with 2 mg and 10 mg bulevirtide in people living with hepatitis delta virus (HDV). These findings build on the wealth of long-term data for the treatment of chronic HDV."

Clinical data • Hepatitis B • Primary Biliary Cholangitis

EFFICACY AND SAFETY OF TREATMENTS FOR CHRONIC HEPATITIS D: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 19 RANDOMIZED CONTROLLED TRIALS (DDW 2025) - "Objective: This meta-analysis evaluates the efficacy and safety of pharmacological treatments for chronic HDV, including Lamivudine, Peg-IFN, Ribavirin, IFN alfa-2a, Adefovir, Bulevirtide, Lonafarnib, TDF, and Entecavir... Bulevirtide with Peg-IFN is the most effective and safest treatment for chronic HDV, particularly in cirrhotic patients. TDF shows potential but requires further study in larger, long-term trials. Adverse effects from therapies like Peg-IFN and Lonafarnib emphasize the need for careful monitoring."

Retrospective data • Review • Anemia • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Pain

HEPATITIS D; AN ORPHAN DISEASE THAT NEEDS EARLY DIAGNOSIS AND TREATMENT (DDW 2025) - "She was able to obtain bulevirtide (2 mg) from Russia but had no virological or biochemical response after 4 months... With increased awareness of HDV screening since 2011, the overall HDV screening rate in our tertiary Liver Center was 50% among CHB patients. In this predominantly foreign CHB cohort, 1.35% were anti-HDV(+) and >40% had cirrhosis at the time of diagnosis. Early diagnosis and effective therapeutic options are urgently needed for this challenging disease."

Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation

MPR_BD: Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Outcomes and Response to Bulevirtide Treatment (clinicaltrials.gov) - P=N/A | N=192 | Recruiting | Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Inflammation

Suboptimal performances of Baveno VII and AASLD 2024 criteria for detecting clinically significant portal hypertension with varices in untreated patients with HDV cirrhosis (EASL 2025) - "EGD and LSM were performed prior to Bulevirtide (BLV) start... Baveno VII and AASLD criteria based on NITs, including SSM, to identify CSPH with EV in CHD demonstrate suboptimal performances compared to other liver disease etiologies. Avoiding screening endoscopy based on NITs in CHD patients could lead to misclassify patients who have varices and are at higher risk of decompensating events."

Clinical • Late-breaking abstract • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Portal Hypertension

Preclinical profiling of ABI-6250, a first-in-class oral therapeutic candidate for chronic hepatitis (EASL 2025) - "Bulevirtide (BLV), an injectable peptide inhibiting HDV entry via binding to the sodium taurocholate co-transporting peptide (NTCP) receptor (a bile acid [BA] transporter) is approved in Europe for the treatment of cHDV. ABI-6250, a highly potent and selective orally bioavail- able first-in-class HDV entry inhibitor, has demonstrated promising preclinical results. ABI-6250 elevates total BAs in monkeys at projected clinically-relevant concentrations without raising CP-I plasma levels, indicating selective NTCP target engagement. ABI- 6250's preclinical PK profile supports once-daily oral dosing for cHDV treatment, and a Phase 1a clinical trial is currently ongoing."

Late-breaking abstract • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Respiratory Syncytial Virus Infections • ABCB1 • SLC22A1

Final results of MYR301: a randomised phase 3 study evaluating the efficacy and safety of up to 144 weeks of bulevirtide monotherapy for chronic hepatitis delta and 96 weeks of posttreatment follow-up (EASL 2025) - "In patients with CHD treated with BLV monotherapy for 96W or 144W, response rates decreased after treatment discontinu- ation. However, a subset of patients maintained undetectable HDV RNA for 2 years posttreatment, which was associated with longer duration of continuous on-treatment undetectability. Posttreatment viral relapse occurred only in the first year after EOT and may be associated with hepatitis flares."

Clinical • Late-breaking abstract • Monotherapy • P3 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D. (PubMed, Liver Int) - "Quantification of L-HBs and of S-HBs, along with HDV-RNA, may reflect the burden of circulating infectious virions in HBV/HDV co-infection, providing a promising tool to identify patients more likely to respond to BLV."

Biomarker • Journal • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation

Incidence of Viral Hepatitis D Relapses Upon Discontinuation of Bulevirtide in Patients With Chronic Hepatitis D and Negative HDV RNA (clinicaltrials.gov) - P=N/A | N=24 | Completed | Sponsor: Center of target therapy | Recruiting ➔ Completed | N=50 ➔ 24

Enrollment change • Trial completion • Hepatology • Infectious Disease • Inflammation

Health-related quality of life in patients with chronic hepatitis D receiving bulevirtide and pegylated interferon: interim results from the SEE-D clinical trial (EASL 2025) - No abstract available

Clinical • HEOR • Hepatology • Inflammation

Gilead: Achievable toDay: Expert insights on HDV patient management (EASL 2025) - "Sponsored by Gilead. To increase healthcare providers' knowledge in the use of bulevirtide by providing an expert perspective on key selected topics and scenarios, including approaches to patient screening, treatment eligibility in paediatric and adult populations, treatment initiation, on-treatment considerations and treatment optimisation."

Clinical • Hepatology • Pediatrics

Screening of different species reveals cat as a potential HBV infection model (EASL 2025) - "Antiviral drug testing included Myrcludex B, Entecavir, and poly IC. This study demonstrates for the first time that primary cat hepatocytes support HBV infection, providing a potential new platform for HBV basic and translational research. The use of cats as an animal model is being explored and may further advance HBV research and therapeutic development."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

Developing personalised treatment pathways for hepatitis B using novel assays and fine needle liver aspirates (EASL 2025) - "By staining cells with fluorescently-labelled myrcludex B (a hepatocyte-specific lipopeptide), we found an average of 3.3 x 105 hepatocytes per FNA... We have developed highly sensitive and specific assays that can quantify HBV cccDNA and iDNA in minimally invasive liver FNAs. We will determine how well intrahepatic cccDNA and/or iDNA predict clinical outcomes after stopping antiviral therapy. We will also assess the correlation and performance of novel blood biomarkers as surrogate markers for HBV activity and host antiviral immune response."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • Pain

The clinical characteristics and antiviral treatment status among chronic HBV mono and HDV co-infected patients (EASL 2025) - "Only 0.6% (n = 3) of the co-infected group were on antiviral treatment for HDV, including Peg-Interferon and Bulevirtide... Our study revealed that individuals with HBV+HDV co-infection have a higher rate of LC compared to those with mono HBV infection. Regarding the treatments for HBV and HDV, among those with mono HBV infection, only 33.3% are currently on NUC treatment while only 0.6% of HBV+HDV co-infected participants on antiviral treatments including peg-IFN and BLV. The elevated liver function indicators and the higher incidence of cirrhosis in HBV and HDV-infected individuals emphasize the urgent need for treatment against HDV."

Clinical • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Immunology • Liver Cancer • Liver Cirrhosis • Oncology • Solid Tumor

Virological response and safety of combination treatment with bulevirtide and pegylated interferon in chronic hepatitis D patients with advanced fibrosis/cirrhosis: 48 weeks interim results from SEE-D trial (EASL 2025) - No abstract available

Clinical • Metastases • Fibrosis • Hepatology • Immunology • Inflammation

Treatment response to bulevirtide leads to improvement of portal hypertension in patients with chronic hepatitis D virus infection: results from the prospective IMPHROVE-D study (EASL 2025) - No abstract available

Clinical • Cardiovascular • Hepatology • Infectious Disease • Inflammation • Portal Hypertension

Long risk of decompensation and HCC in patients with HDV-related compensated cirrhosis treated with Bulevirtide monotherapy for up to 144 weeks: the retrospective multicenter european study (Save-D) (EASL 2025) - No abstract available

Monotherapy • Retrospective data • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology

A marker of cccDNA transcription - hepatitis B core-related antigen (HBcrAg) - mimics HBV RNA decline during antiviral therapy with bulevirtide in chronic hepatitis delta (HDV) patients (EASL 2025) - "Of several novel HBV biomarkers only HBcrAg levels mirrored HDV RNA decline during antiviral therapy with BLV, in contrast to no changes in levels of HBsAg and pgRNA. Larger studies assessing the role of HBcrAg during HDV therapy would be beneficial."

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

HDV infection induces cellular refractoriness to IFN-ɑ, but not IFN-λ treatment (EASL 2025) - "Current therapies available in Europe include the entry inhibitor bulevirtide and pegylated interferon-alpha (peg-IFN-α)... Our findings provide a comprehensive list of ISGs modulated by type I and type III IFN treatments in the context of HDV infection. We demonstrated that the cellular refractoriness to IFN-α treatment in HDV-infected cells results from the pre-activation of the innate immune response by HDV and is specific to the type I IFN pathway. In this context, USP18 acts as a negative regulator of the IFN-α response and is a key factor in HDV resistance to IFN-α treatment."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFIH1 • IFNA1 • USP18

Epigenetic viral footprint of chronic HDV infection in HBV co-infected chimeric mice (EASL 2025) - "We have uncovered an HDV-specific transcriptional signature that may be part of a persistent epigenetic viral footprint. Components of the signature are differentially secreted into the blood of infected animals and may therefore serve as risk markers for disease progression. Further work is underway to determine whether these proteins can serve as prognostic biomarkers for disease progression and/or therapeutic response, such as bulevirtide, and to predict and validate compounds capable of reversing risk-associated transcriptional signatures."

Preclinical • Fibrosis • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Oncology • Solid Tumor

A novel orally bioavailable small-molecule inhibitor of the sodium taurocholate co-transporting polypeptide (NTCP) prevents HBV infection and ameliorates cholestasis in humanized mice models (EASL 2025) - "Daily injection with a synthetic peptide called bulevirtide (previously Myrcludex-B) is approved in the EU for treatment of patients co-infected with HBV and HDV... We describe novel and specific small-molecule orally bioavailable NTCP inhibitors that have the potential to treat HBV/HDV and cholestatic liver disease."

Preclinical • Cholestasis • Genetic Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Primary Immunodeficiency

Patient characteristics and treatment patterns amongst hepatitis D patients: results from a real-world survey in Europe (EASL 2025) - "Background and Aims: While data are readily available on antiviral drugs treating hepatitis B virus (HBV), real-world evidence on bulevirtide (BLV) – the first antiviral drug for the treatment of hepatitis D virus (HDV) – is lacking... Analysis of physicians' data showed that half of the patients with chronic HDV had a high comorbidity burden, most HDV treated patients received BLV monotherapy, and the majority were adherent to treatment. Prescribers treat HDV with BLV or IFN due to their long-term efficacy in reducing viral shedding and transmission. Physicians reported a remaining unmet need for longer-acting medication with a less frequent dosing schedule and further research is needed into factors affecting high patient adherence to BLV."

Clinical • Real-world • Real-world evidence • Diabetes • Fibrosis • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Disorders • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Adaptive NK cells are expanded in CMV-positive patients with chronic hepatitis B or hepatitis D and remain elevated after initiation of antiviral treatment (EASL 2025) - "Follow-up samples after initiation of antiviral therapy (Tenofovir / Entecavir for HBV monoinfected, Hepcludex for HBV/HDV coinfected) were available for eight HBV and eight HBV/HDV coinfected patients. Chronic viral hepatitis B induces high level FcepsilonRIgamma(-) CD56dim cell expansions in CMV+ individuals and this does not change after initiation of therapy with nucleoside/nucleotide inhibitors. Adaptive NK cells have an activated profile and predominantly effector functions compared to non-adaptive NK cells. We hypothesise that the higher cytotoxic activity and high CD95 expression may be involved in the development of liver fibrosis."

Clinical • Cytomegalovirus Infection • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • B3GAT1 • CD69 • FAS • FCER1G • GZMB • IFNG • IL2RA • LAMP1