Hepcludex (bulevirtide) / Hepatera, Gilead - LARVOL DELTA

Evolving insights into viral hepatitis: Advances, evidence, and expert perspectives from the ESCMID Study Group for Viral Hepatitis (ESGVH) - Part 2: hepatitis B, C, and delta. (PubMed, Germs) - "HDV epidemiology is evolving, and is being increasingly studied; in parallel, the approval of bulevirtide represents a major breakthrough in therapy, with further agents in the HDV pipeline. For HCV, direct-acting antivirals provide curative therapy and have made elimination a realistic goal, while identifying remaining gaps in diagnosis, linkage-to-care, and equitable access offers clear opportunities to accelerate progress. Together, these advances bring the goal of a hepatitis-free future closer than ever."

Journal • Review • Fibrosis • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor

Development of a CRE/CREB-driven HBx responsive HBV cell culture reporter system for antiviral drug evaluation. (PubMed, JHEP Rep) - "In contrast, antivirals that do not interfere with protein production (tenofovir), or viral entry (bulevirtide) showed no effect (p <0.05), underscoring the specificity of the system for identifying compounds that inhibit protein production and/or HBx function...Its ability to detect HBx activity from both laboratory and clinical HBV isolates underscore its translational relevance. By enabling selective screening of HBx-targeting agents, this system may advance efforts to silence covalently closed circular DNA and accelerate the development of curative therapies for chronic hepatitis B."

Journal • Preclinical • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Leukemia • Oncology • IFNA1

Bulevirtide Monotherapy or in Combination for Chronic Hepatitis Delta: 2025 Update. (PubMed, J Viral Hepat) - "EMA recommends proceeding with BLV therapy until proven clinical benefit, without further details on this topic. This review synthesizes current evidence on BLV's efficacy effectiveness and safety profile, both as monotherapy and in combination with PegIFNα, drawing from clinical trials and real-world studies, with the aim to propose treatment strategies aligned with disease severity and patients' profile."

Journal • Monotherapy • Review • Fibrosis • Hepatitis B • Hepatocellular Cancer • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Liver Failure • Oncology • Solid Tumor • IFNA1

Study of Bulevirtide in Participants With Chronic Hepatitis D Infection (clinicaltrials.gov) - P=N/A | N=170 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2027 ➔ Jul 2028 | Trial primary completion date: Nov 2027 ➔ Jul 2028

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

Bulevirtide for chronic hepatitis delta: from clinical trials to real life data: an expert opinion report. (PubMed, Antiviral Res) - "We need new finite therapies. Further real-world data and newer therapies are required for this severe disease."

Journal • Review • Fibrosis • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Transplantation

Novel mechanism of Guizhi Jia Huangqi Decoction disrupting HBV lifecycle via cAMP/PKC/PKB axis beyond NTCP blockade. (PubMed, J Ethnopharmacol) - "GZHQ effectively inhibited HBV invasion by modulating the cAMP/PKC/AKT/NTCP signaling axis and uniquely suppressed cccDNA transcriptional activity. By targeting both viral entry and the cccDNA reservoir, GZHQ demonstrated superior antiviral efficacy in vitro compared to Myrcludex B. These findings warrant further in vivo validation to explore the full pharmacological potential and safety profile of GZHQ as a promising multi-targeted therapy for chronic HBV infection."

Journal • Hepatitis B • Infectious Disease • Inflammation • EGFR • RAB5A

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 (FFS-AIH 2025) - "Daily injection with a peptide inhibitor of NTCP, 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 • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Primary Immunodeficiency

Treatment outcomes of Peg-interferon alpha-2a in patients with chronic HDV infection (FFS-AIH 2025) - "Despite the approval of bulevirtide for HDV treatment, its high cost and limited efficacy (around 20%) remain major barriers... Peg-IFN demonstrated notable antiviral and antifibrotic effects in patients with chronic HDV infection, with a manageable safety profile. It remains a viable treatment option, especially in resource-limited settings. Keywords: HDV-RNA – Hepatitis D viral load, q-HBsAg – Hepatitis B surface antigen, HDV – Hepatitis D virus, HBV – Hepatitis B virus"

Clinical • Alopecia • Fatigue • Fibrosis • Hematological Disorders • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Leukopenia • Liver Cirrhosis • Solid Tumor

Crossing Borders for Organs: A Case of Transplant Tourism (KIDNEY WEEK 2025) - "She was given cyclosporine, mycophenolate, and prednisolone, without prophylactic antimicrobials or transplant education...Decompensated liver disease: Prior to transplant, her HBV and HDV were well controlled on tenofovir alafenamide and bulevirtide...As recipients return home, the responsibility of care falls on local transplant physicians, raising ethical concerns about beneficence versus a sense of complicity in organ trade. Physicians should document transplant circumstances, consult ethics, and ensure continued care even if it warrants transferring the patient."

Clinical • Cardiovascular • Chronic Kidney Disease • Cough • Cytomegalovirus Infection • Glomerulonephritis • Hepatitis B • Hepatology • Infectious Disease • Influenza • Lupus Nephritis • Nephrology • Respiratory Diseases • Solid Organ Transplantation • Transplantation • Tuberculosis • Urinary Incontinence • ERBB3

Safety and efficacy of REP 2139-Mg in patients with HDV-related advanced liver disease in an international compassionate access program. (PubMed, J Hepatol) - P | "REP treatment was safe and effective in HDV patients with ACLD. REP may even induce HDV sustained virological response and HBV functional cure independent of combination with pegIFN. Clinical benefits may also be observed in patients with decompensated cirrhosis."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Transplantation

Hepatitis B virus is a stealth virus that minimizes proteomic and secretomic changes in primary human hepatocytes. (PubMed, J Gen Virol) - "We used HBV infection in the presence of the entry inhibitor bulevirtide as a control to separate the effects of productive infection from those caused by inoculum-associated components...Knockdown had no impact on viral RNA or antigen levels, suggesting that the observed proteomic changes may reflect stress responses or broader modulation of the hepatic microenvironment. Our findings support the concept of HBV as a stealth virus and underscore the importance of carefully controlled experimental systems for studying host responses to infection in vitro."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Predictors of Undetectable Hepatitis Delta Virus RNA at 48 Weeks After End of Treatment With Bulevirtide Monotherapy in the MYR 301 Study (ACG 2025) - "Baseline (BL) characteristics were similar between treatments. Overall, 65/149 (44%) pts achieved HDV RNA undetectability at EOT; 23/64 (36%) with FU data sustained undetectability through FU48. Sustained undetectability rates were higher in the immediate treatment arms (2 mg: 7/14, 50%; 10 mg: 10/25, 40%) vs the DT/10 mg (6/26, 23%) arm."

Monotherapy • Fibrosis • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation

Achieving Undetectable Hepatitis Delta Virus RNA at End of Therapy With Bulevirtide 10 Mg/day With or Without PegIFNα Is Strongly Associated With Posttreatment Virologic Response in Chronic Hepatitis Delta (ACG 2025) - "Demographics were similar across groups (Table). At EOT, 49% (97/200) achieved undetectable HDV RNA: (A) 70% (35/50), (B) 37% (37/100), and (C) 50% (25/50); 24% (48/200) had < LLOQ, TD: (A) 16% (8/50), (B) 30% (30/100), and (C) 20% (10/50; Figure). At FU48, undetectable HDV RNA was observed in 25% (49/200) overall: (A) 23/50 (46%) of pts receiving combination therapy, (B) 14% (14/100) of pts receiving 2 years of BLV monotherapy, and (C) 24% (12/50) of pts receiving 3 years of BLV monotherapy."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

Final Results of MYR301: A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Up to 144 Weeks of Bulevirtide Monotherapy for Chronic Hepatitis Delta and 96 Weeks of Post-Treatment Follow-Up (ACG 2025) - "Most patients (92%) remained in the study at the end of treatment (EOT); 72% and 57% completed FU48 and FU96, respectively. CR rates in the 2, 10, and DT to 10 mg groups, respectively, declined from 57%, 54%, and 56% at EOT to 24% in each group at FU96. HDV RNA undetectability rates were 29%, 50%, and 52% at EOT and 20%, 22%, and 20% at FU96."

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

NTCP ubiquitination enables HBV infection. (PubMed, JHEP Rep) - "The global ubiquitination inhibitor TAK-243 was used to study effects on uptake and HBV infection in NTCPWT-HepG2 and HepaRG cells...In addition, a K at position 340 was identified as the main ubiquitination target of NTCP; ubiquitination-mediated endocytosis of NTCP at this position is likely to be the mechanism regulating HBV internalization. Thus, interfering with NTCP ubiquitination could provide a novel means to reduce HBV infection."

Journal • Hepatitis B • Infectious Disease • Targeted Protein Degradation

Current evidence of bulevirtide as monotherapy compared to combination treatment with pegylated interferon for hepatitis delta. (PubMed, Expert Rev Anti Infect Ther) - "In addition, long-term therapy appears to enhance response rates and may even promote the loss of HDV-infected hepatocytes, potentially leading to a sustained off-therapy response. However, new therapeutic strategies are needed for patients who do not respond."

Journal • Monotherapy • Review • Hepatology • Immunology • Infectious Disease • Inflammation

Impact of Handling Perception and Language Barriers on Virologic Response to Daily Subcutaneous Bulevirtide in Hepatitis D. (PubMed, Liver Int) - "BLV administration is generally well manageable. Limited language proficiency and injection difficulties may negatively affect patient satisfaction and potentially influence treatment outcomes."

Journal • Hepatology • Inflammation

EFFICACY AND SAFETY OF BULEVIRTIDE WITH OR WITHOUT PEGYLATED INTERFERON IN THE TREATMENT OF CHRONIC HEPATITIS D: A SYSTEMATIC REVIEW AND META-ANALYSIS WITH META-REGRESSION (UEGW 2025) - "Bulevirtide combined with pegylated interferon is more effective than monotherapy in achieving undetectable HDV RNA at 24 weeks. No dose-dependent effect of bulevirtide on virological response was observed. Further studies are needed to validate these findings and evaluate the long-term safety and efficacy of this combination therapy."

Retrospective data • Review • Fibrosis • Hepatology • Infectious Disease • Inflammation

Applying the COM-B Model to Identify Barriers to Bulevirtide Adherence in Chronic Hepatitis D: A Multicenter Italian Study. (PubMed, J Viral Hepat) - "Specifically, 10% had considered discontinuing treatment and 10% admitted to having missed doses. A deeper understanding of these multifactorial determinants may aid in the development of targeted interventions to enhance adherence and achieve personalized therapeutic outcomes for individuals living with HDV."

Journal • Infectious Disease • Inflammation

A NEW CLASS OF ORALLY AVAILABLE NTCP INHIBITORS DEMONSTRATES POTENT EFFICACY AGAINST HBV AND CHOLESTASIS IN HUMANIZED MICE MODELS (AASLD 2025) - "Daily injection with a Pre-S1 mimicking synthetic peptide called bulevirtide (also called 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

RATES OF HDV RNA UNDETECTABILITY DURING LONG-TERM BULEVERTIDE MONOTHERPAY IN PATIENTS WITH CHD ARE ASSAY-DEPENDENT (AASLD 2025) - "Background: A recent pooled analysis from the MYR2 204 and MYR301 studies suggested that, in patients with compensated CHD, the achievement of undetectable HDV RNA at EOT predicts maintaining undetectable viremia in the posttreatment period... The proportion of patients achieving HDV RNA TND during long-term BLV monotherapy significantly differed according to the quantification assay used. These findings call attention to the urgency for further studies in this clinical setting to adequately identify patients who could safely withdraw BLV monotherapy."

Clinical • Fibrosis • Hepatology • Immunology

PERSISTENT LOW VIREMIC RELAPSE VS HIGH VIREMIC RELAPSE AFTER THE END OF TREATMENT WITH BULEVIRTIDE WITH OR WITHOUT PEGYLATED INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS DELTA VIRUS (AASLD 2025) - P2, P3 | "Most pts treated with BLV alone or in combination with PegIFNα who achieved undetectable HDV RNA at EOT either sustained undetectable HDV RNA posttreatment or had high viremic relapse, which was associated with loss of biochemical response. However, a small subset of pts had only low-level virological relapse (<50 units) and maintained biochemical response; there was no progression to high viremic relapse after 1 year. The clinical significance of low-level viremia in the posttreatment period remains to be elucidated."

Clinical • Hepatology • Infectious Disease • Inflammation • IFNA1

EFFECT OF 48-WEEK BULEVIRTIDE THERAPY ON NON-INVASIVE MARKERS OF LIVER FIBROSIS IN PATIENTS WITH HBEAG NEGATIVE CHRONIC HEPATITIS B/D (AASLD 2025) - "Treatment with BLV for 48 weeks is associated with a reduction in the NIT's particularly in LS values by transient elastography. Changes in NIT's based on serology (APRI and FIB-4) are clearly related to the biochemical response; therefore the profile of biochemistry during treatment should be taken into account when evaluating progression / regression of liver disease with APRI or FIB-4."

Clinical • Non-invasive • Fibrosis • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

INTEGRATED VIROLOGY ANALYSIS OF BULEVIRTIDE (BLV) MONOTHERAPY IN CHRONIC HEPATITIS DELTA: POOLED DATA THROUGH 96 WEEKS OF TREATMENT (AASLD 2025) - "BLV monotherapy demonstrated efficacy in patients with chronic HDV, including those with HBV GTD and GTA. Integrated virology and resistance analysis through Week 96 did not identify genotypic or phenotypic resistance to BLV, supporting its continued use as a monotherapy for the treatment of HDV infection."

Monotherapy • Hepatology • Infectious Disease • Inflammation

SAFETY, EFFECTIVENESS AND CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC HEPATITIS DELTA TREATED WITH BULEVIRTIDE MONOTHERAPY: A POOLED ANALYSIS ON 689 PATIENTS ENROLLED IN THE SAVE-D AND D-SHIELD STUDIES (AASLD 2025) - "BLV monotherapy 2 mg/day confirmed effectiveness and safety in two large multicenter cohorts of real-world CHD patients, independently of baseline cirrhosis. Lower baseline HDV RNA levels predicted HDV RNA undetectability at week 48. VBK and liver-related events occurred in few patients only."

Clinical data • Monotherapy • Retrospective data • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis