Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-negative chronic hepatitis B infection

Fung, Scott; Sulkowski, Mark S.; Jp, Lalezari; Schiff, E.; Dieterich, D T; Hassanein, Tarek; Kwo, P.; Elkhashab, Magdy; Nahass, Ronald; Ayoub, Walid; Han, SH; Bonacini, Maurizio; Alves, Katia; Zayed, Hania S.; Huang, Qi; Colonno, Richard; Knox, Steven J.; Ramji, A.; Bennett, MK; Gane, Ed; Ravendhran, Natarajan; Park, J; Jacobson, Ira M.; Bae, Ho; Chan, Sing; Hann, HW; Ma, Xiao; Nguyen, Thang; Yuen, Rmf

doi:10.1016/s0168-8278(20)30649-8

Cited by 10 publications

(12 citation statements)

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“…HBV RNA concentrations are low at baseline in HBeAg‐negative cohorts. Somewhat similar findings were observed in recent phase 2 extension studies of ABI‐H0731 32,33 . The population‐dependent reductions in HBsAg may be mainly because of the reduction in HBsAg from Dane particles.…”

Section: Inhibitors Of Hbv Replicationsupporting

confidence: 85%

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Hepatitis B cure: How and when

Dusheiko

2021

Liver International

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Background First‐ and second‐ generation new treatments are being evaluated to provide a cure for hepatitis B. The life cycle of HBV includes several well‐ categorized steps that are targets for new treatments. A cure remains a major challenge even if it is measured by HBsAg seroclearance alone. The notion of a functional cure of hepatitis B has been accepted, while a partial functional cure has been more tentatively defined as a decline in HBsAg concentrations to lower levels after finite treatment. Methods More profound suppression of hepatitis B replication through the addition of capsid inhibitors with nucleoside analogues could improve patient prognosis and a sustained treatment response. Several strategies are being evaluated to achieve a cure: (a) deepening inhibition of HBV replication or (b) a reduction in HBsAg presentation for HBsAg seroclearance. Results Fortunately, there are signs of important progress in the treatment of hepatitis B including improved on‐ treatment reductions or seroclearance of HBsAg in phase 2 studies that was not achieved with chain terminators and inhibitors of initiation of DNA synthesis. Progress in immunomodulatory therapy has lagged behind that of antiviral therapy. Conclusions Increasing the multilayered impaired and dysfunctional immune response in hepatitis B is perhaps more likely and feasible after a reduction in host antigen burden. Other potential experimental strategies include CRISPR‐ Cas9 genome‐ editing nucleases to specifically target and cleave cccDNA or novel monoclonal antibodies.

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Section: Inhibitors Of Hbv Replicationsupporting

confidence: 85%

“…Somewhat similar findings were observed in recent phase 2 extension studies of ABI-H0731. 32,33 The population-dependent reductions in HBsAg may be mainly because of the reduction in HBsAg from Dane particles. This suggests that the "primary" mechanism of action could predominate.…”

Section: Inhib Itor S Of Hbv Repli C Ati Onmentioning

confidence: 99%

Hepatitis B cure: How and when

Dusheiko

2021

Liver International

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“…Preliminary results on ARC-520, a siRNA targeting cccDNA-derived transcription, suggest a reduction in antigen production driven by cccDNA in HBeAg-positive patients, with a smaller decline in qHBsAg compared to HBcrAg in HBeAg-negative patients [70]. A CAM, ABI-H0731 (Vebicorvir), administered with NAs in HBeAg-negative patients resulted in undetectable HBV-RNA in all cases at week-24 [71]. Among naïve HBeAg-positive CHB patients, Vebicorvir J o u r n a l P r e -p r o o f plus NAs resulted in deep on-treatment viral suppression than that achieved by NAs alone.. Another CAM, JNJ 6379 (at either 75 mg or 250 mg) combined with NAs for 24 weeks has been evaluated in HBeAg-positive and HBeAg-negative patients [72].…”

Section: New Drugsmentioning

confidence: 99%

How to interpret viral markers in the management of chronic hepatitis B infection

Riveiro‐Barciela

Pericàs

Buti

2022

Clinical Microbiology and Infection

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“…Preliminary results have confirmed the favourable safety profile of ABI‐H0731. Moreover, after 24 weeks of treatment, a higher proportion of hepatitis B e antigen (HBeAg)‐negative patients receiving ABI‐H0731/NUC achieved undetectable HBV DNA levels compared to the placebo/NUC group 14 . The results of at least three other CAMs, JNJ‐6379, GLS4 and RO7049389, have been favourable in phase I trials and are being evaluated in phase II studies (NCT03361956, NCT0414720 and, NCT04225715) 15,16 …”

Section: Novel Direct‐acting Antivirals Against Hbv Infectionmentioning

confidence: 99%

HBV 2021: New therapeutic strategies against an old foe

Suarez

Testoni

Zoulim

2021

Liver International

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Hepatitis B virus (HBV) affects more than 250 million people worldwide, and is one of the major aetiologies for the development of cirrhosis and hepatocellular carcinoma (HCC). In spite of universal vaccination programs, HBV infection is still a public health problem, and the limited number of available therapeutic approaches complicates the clinical management of these patients. Thus, HBV infection remains an unmet medical need that requires a continuous effort to develop new individual molecules, treatment combinations and even completely novel therapeutic strategies to achieve the goal of HBV elimination. The following review provides an overview of the current situation in chronic HBV infection, with an analysis of the scientific rationale of certain clinical interventions and, more importantly, explores the most recent developments in the field of HBV drug discovery.

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Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-negative chronic hepatitis B infection

Cited by 10 publications

References 0 publications

Hepatitis B cure: How and when

Hepatitis B cure: How and when

How to interpret viral markers in the management of chronic hepatitis B infection

HBV 2021: New therapeutic strategies against an old foe

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