REP 2139 / Replicor - LARVOL DELTA

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

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

Chronic Hepatitis D Virus Infection and Its Treatment: A Narrative Review. (PubMed, Microorganisms) - "These newer antiviral therapies include buleviritide (which blocks HDV entry), lonafarnib (which prevents HDV assembly), and REP-2139 (which prevents HDV export). In this manuscript, we discuss the characteristics of HDV infection and review the new antiviral therapies approved for treatment and those under investigation."

Journal • Review • Fibrosis • Hematological Disorders • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Neutropenia • Oncology • Psychiatry • Solid Tumor • Thrombocytopenia

CHARACTERIZATION OF THE DIRECT ANTIVIRAL EFFECT OF REP 2139 IN 2D AND 3D HDV INFECTION MODELS (AASLD 2024) - "REP 2139 has a direct antiviral effect against HDV RNA replication that involves a block of HDV RNA interaction with HDAg during the morphogenesis of the HDV RNP. The establishment of the 3D PCLS model paves the way to further mechanistic studies and the investigation of REP 2139 in combination therapies."

Hepatology • Infectious Disease • DNAJB1

Compassionate use of REP 2165-Mg in chronic HBV/HDV patients with progressive liver disease and failure to previous pegIFN therapy (EASL-ILC 2024) - "Background and Aims: REP 2165 is an analog of REP 2139 no longer in development with identical activity to REP 2139 in HBV and HDV in clinical studies (achieving HBV functional cure and HDV cure) but with weaker liver accumulation. Although REP 2165-Mg is no longer in clinical development, it demonstrates excellent safety and efficacy against HBV and HDV infection in patients with advanced liver disease with prior pegIFN failure. These results confirm previous clinical data, expand the database of NAP compassionate use and inform on the design of upcoming phase IIA studies."

Clinical • Fibrosis • Hepatitis B • Hepatology • Immunology

Safety and efficacy of REP 2139-Mg in hepatitis D patients with advanced liver disease: an international compassionate use program (EASL-ILC 2024) - P=N/A | " Of 33 patients (21-69 y.o.), 24 failed previous pegIFN, 20 failed previous bulevirtide+/-pegIFN (11 with viral rebound during therapy) and 1 failed lonarfarnib. REP 2139-Mg was safe and well tolerated in HDV patients with advanced liver disease and can lead to HDV cure and HBV functional cure. REP 2139-Mg treatment can lead to HDV cure independently of pegIFN, while HBV functional cure may be pegIFN dependent."

Clinical • Metastases • Fibrosis • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Antiviral efficacy of REP 2139-Mg and effects on HVPG in HDV/HBV coinfected patients with cirrhosis and portal hypertension non-responding to previous bulevirtide treatment (EASL-ILC 2024) - P=N/A | "Weekly REP 2139-Mg in combination with TDF and low-dose pegIFN appeared safe and effective against HBV/HDV infection in patients with cirrhosis and CSPH. Potential ALT flares should be monitored closely but may reflect an immune response triggering the subsequent decrease/loss of HDV-RNA and of HBsAg – as observed in 2 out of our 3 patients. Portal hypertension may remain controlled despite ALT flares during REP 2139-Mg therapy in patients with CSPH."

Clinical • Cardiovascular • Dermatology • Fibrosis • Hepatitis B • Hepatology • Immunology • Inflammation • Portal Hypertension • Pruritus

SAFETY AND EFFICACY OF REP 2139-MG AGAINST HBV / HDV CO-INFECTION WITH ADVANCED LIVER DISEASE (DDW 2024) - P=N/A | "Compassionate use of subcutaneously administered REP 139-Mg (Replicor Compassionate Access Program RCAP [NCT05683548]) is underway in cirrhotic HBV / HDV co-infection with HDV non-response or viral rebound during previous therapy with pegIFN and or bulevirtide (BLV). ConclusionsREP 139-Mg is safe and effective against HBV/HDV infection in advanced liver disease and in patients with additional HIV co-infection. REP 139-Mg can clear HDV RNA from the blood and liver and can establish HBV functional cure and HDV cure in advanced liver disease."

Clinical • Metastases • Fibrosis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Transplantation

Recent treatment advances and practical management of hepatitis D virus. (PubMed, Clin Med (Lond)) - "This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease."

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

Rescue of Cirrhotic HBV / HDV Infection from Bulevirtide Failure by Subcutaneous REP 2139-mg (APASL 2023) - "Subcutaneous REP 2139-Mg is safe, well tolerated, and effective against HBV and HDV infection in combination with TDF and low dose pegIFN in patients with compensated cirrhosis. REP 2139-Mg is also an effective salvage therapy in bulevirtide failure patients. 712"

Fibrosis • Genetic Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Obesity

Compassionate Use of Rep 2139-Mg in HBV/Hdv infection with Advanced Liver Disease (APASL 2024) - P=N/A | "An ongoing compassionate use program (NCT05683548) provides REP 2139-Mg therapy for cirrhotic HBV / HDV co-infection with viral nonresponse or rebound with pegIFN and or bulevirtide therapy. REP 2139-Mg is safe and effective against HBV/HDV infection in advanced liver disease. REP 2139-Mg can clear HDV RNA from the blood and liver and can establish HBV functional cure and HDV cure in advanced liver disease."

Metastases • Fibrosis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease

New Paradigm of Delta Infection (APASL 2024) - "There are no current treatments in the United States (US) that 40 are Food and Drug Administration (FDA)-approved for the treatment of HDV; and one approved therapy in the EU by the EMEA with conditional approval; however, bulevirtide and is under review with the US FDA...There are other therapies in development globally that have shown promise, including lonafarnib (LNF) and the NAP: REP 2139...Others 3. Coinfection of Viral Hepatitis and HIV"

Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients. (PubMed, Antiviral Res) - "Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients...REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy...In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders."

Journal • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Pangenomic antiviral effect of REP 2139 in CRISPR/Cas9 engineered cell lines expressing hepatitis B virus surface antigen. (PubMed, PLoS One) - "The secretion of HBsAg was confirmed into these new genotype cell lines (GCLs) and the antiviral activity of the NAP REP 2139 was then assessed. The results demonstrate that REP 2139 exerts an antiviral effect in all genotypes and serotypes tested in this study, including the vaccine escape mutant, suggesting a pangenomic effect of the NAPs."

Journal • Preclinical • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor

PANGENOMIC ANTIVIRAL EFFECT OF REP 2139 IN CRISPR/Cas9 ENGINEERED CELL LINES EXPRESSING HEPATITIS B VIRUS HBsAg (AASLD 2023) - "CRISPR/Cas9 was used to create in vitro HepG2-derivative cell lines expressing HBsAg from various genotypes and serotypes. Our results suggest that REP 2139 has a pangenomic antiviral effect, as well as an antiviral effect for vaccine escape mutants."

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

CHARACTERIZATION OF THE DIRECT ANTIVIRAL EFFECT OF REP 2139 ON HDV REPLICATION (AASLD 2023) - "REP 2139 has a direct acting antiviral effect against HDV RNA replication which may involve blocking HDV RNA interaction with HDAg during the morphogenesis of HDV RNP. These antiviral effects bear further investigation and may explain the more rapid decline of HDV RNA versus HBsAg in human studies."

Hepatitis B • Hepatology • Infectious Disease • Inflammation

TREATMENT WITH REP 2139-MG IN ASSOCIATION WITH TDF IN HDV DECOMPENSATED CIRRHOSIS IS SAFE AND EFFECTIVE IN A REAL-LIFE SETTING (AASLD 2023) - "REP 2139-Mg is safe and well tolerated in CHD patients with decompensated cirrhosis. HBV-HDV functional cure appears achievable for the first time in this special population, which could prevent the need for liver transplant."

Clinical • Cardiovascular • CNS Disorders • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Hypertension • Immunology • Infectious Disease • Oncology • Portal Hypertension • Solid Tumor • Transplantation

SAFETY AND EFFICACY OF REP 2139-MG-BASED THERAPY IN FRENCH PATIENTS WITH PRIOR FAILURE TO PEGIFN AND OR BULEVIRTIDE (AASLD 2023) - P=N/A | "Subcutaneous REP 2139-Mg is safe, and effective against HBV and HDV infection in combination with TDF and low dose pegIFN in patients with compensated cirrhosis and can salvage failure from BLV therapy."

Clinical • Dermatology • Fibrosis • Gastroenterology • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure

SAFETY AND EFFICACY OF REP 2139-MG-BASED THERAPY IN AUSTRIAN PATIENTS WITH HBV / HDV COMPENSATED CIRRHOSIS WITH PRIOR FAILURE TO BULEVIRTIDE (AASLD 2023) - P=N/A | "Subcutaneous weekly REP 2139-Mg in combination with TDF and low-dose pegIFN appears safe and effective against HBV/HDV infection in patients with compensated cirrhosis and CSPH, although the use of pegIFN warrants close clinical/laboratory monitoring. The reductions in HVPG observed in both patients with a hepatitis flare suggest a clinically meaningful amelioration of portal hypertension that may translate into a decreased risk of hepatic decompensation."

Clinical • Cardiovascular • Dermatology • Fibrosis • Hepatitis B • Hepatology • Hypertension • Immunology • Infectious Disease • Inflammation • Liver Failure • Portal Hypertension

AN IN VITRO CULTURE MODEL FOR THE INDUCTION OF HDV REPLICATION IN A HBV EXPRESSING CELL LINE (AASLD 2023) - "This new and unique model will be instrumental for the screening/characterization of new antivirals targeting both viruses (such as REP 2139). The HepG2BD cell line is also expected to help in our understanding of the dynamic interplay between the HBV and HDV lifecycles, and in identifying cellular factors involved."

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

Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet? (PubMed, Curr Issues Mol Biol) - "This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor)."

Journal • Review • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor • Transplantation

Safety and efficacy of REP 2139-Mg in association with TDF in chronic hepatitis delta patients with decompensated cirrhosis (EASL-ILC 2023) - No abstract available

Clinical • Fibrosis • Hepatology • Immunology • Inflammation

Safety and efficacy of REP 2139-Mg in association with TDF in chronic hepatitis delta patients with decompensated cirrhosis (EASL-ILC 2023) - P=N/A | "She had HDV relapse one year after discontinuing bulevirtide 2 mg and pegIFN 180 µg and progressed to decompensated cirrhosis (Child Pugh C11, portal hypertension, ascites and HCC) with accompanying edema and pronounced fatigue. REP 2139-Mg in association with TDF is safe and well tolerated in patients with CHD and decompensated cirrhosis. Liver function improvement with significant ascites reversal was rapid, occurring after only 4 weeks of treatment. HBV-HDV functional cure with HBsAg loss and HBs seroconversion appears achievable for the first time in this special population, which could prevent the need for a future liver transplant."

Clinical • Cardiovascular • CNS Disorders • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Hypertension • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Portal Hypertension • Solid Tumor • Transplantation

Rescue of cirrhotic HBV / HDV infection from bulevirtide failure by subcutaneous REP 2139-Mg (EASL-ILC 2023) - P=N/A | "Subcutaneous REP 2139-Mg is safe, well tolerated, and effective against HBV and HDV infection in combination with TDF and low dose pegIFN in patients with compensated cirrhosis. REP 2139-Mg is also an effective salvage therapy in bulevirtide failure patients."

Fibrosis • Genetic Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Obesity