Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due...Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due to an increased risk for liver cirrhosis,liver failure,and hepatocellular carcinoma relative to HBV monoinfected individuals.The current treatment of chronic HDV infection includes the off-label use of pegylated interferon(IFN),which is limited by poor safety,tolerability,and efficacy.Guidelines of the major international liver organizations such as the American Association for the Study of Liver Diseases,European Association for the Study of the Liver,and Asian Pacific Association for the Study of the Liver provide recommendations for contemporary diagnosis and management of chronic HDV infection,including the incorporation of bulevirtide,a newly licensed antiviral agent in Europe.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.展开更多
Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side eff...Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side effects.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.Recently,several new drugs have entered various stages of development,offering hope for improved hepatitis D virus(HDV)management.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).Emerging trials are now considering combination therapies,such as SOLSTICE,a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran.The combination dosed monthly achieved>50%virologic and biochemical response at 24 weeks of therapy.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.展开更多
文摘Chronic hepatitis delta virus(HDV)represents a rare but important co-infection in approximately 5%of patients with chronic hepatitis B virus(HBV)infection,and is associated with significant morbidity and mortality due to an increased risk for liver cirrhosis,liver failure,and hepatocellular carcinoma relative to HBV monoinfected individuals.The current treatment of chronic HDV infection includes the off-label use of pegylated interferon(IFN),which is limited by poor safety,tolerability,and efficacy.Guidelines of the major international liver organizations such as the American Association for the Study of Liver Diseases,European Association for the Study of the Liver,and Asian Pacific Association for the Study of the Liver provide recommendations for contemporary diagnosis and management of chronic HDV infection,including the incorporation of bulevirtide,a newly licensed antiviral agent in Europe.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.
文摘Current treatment options for hepatitis D are limited,with pegylated interferonalpha(PEG-IFNα)being the only therapy available in the Asia-Pacific region.However,PEG-IFNαhas limited efficacy and significant side effects.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.Recently,several new drugs have entered various stages of development,offering hope for improved hepatitis D virus(HDV)management.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).Emerging trials are now considering combination therapies,such as SOLSTICE,a Phase 2 clinical trial evaluating tobevibart alone or combined with elebsiran.The combination dosed monthly achieved>50%virologic and biochemical response at 24 weeks of therapy.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.
