Safety, pharmacokinetics, and antiviral activity of the class II capsid assembly modulator ALG-000184 in subjects with chronic hepatitis B

Yuen, Man‐Fung; Agarwal, Kosh; Gane, Edward; Jucov, Alina; Schwabe, Christian; Niu, Junqi; Hou, Jinlin; Le, Kha; Massetto, Benedetta; Westland, Christopher; Zhang, Qingling; Lai, F. S.; Venkatraman, Meenakshi; Blatt, Lawrence M.; Lin, Tse‐I; Chanda, Sushmita; McClure, Matt; Fry, J. R.

doi:10.1016/s0168-8278(22)01967-5

Cited by 12 publications

(9 citation statements)

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“…31 According to the present study, EDP-514 appears to have a similar potency of HBV DNA and HBV RNA suppressions when compared with ALG-000184 (mean HBV DNA and HBV RNA reductions of 3.8 log 10 IU/mL and 1.9 log 10 copies/ mL after 4 weeks of treatment, respectively). 32 Whether a longer treatment duration of EDP-514 than 4 weeks could also show an HBsAg reduction would be interesting to explore in the future.…”

Section: Discussionmentioning

confidence: 99%

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients

Yuen,

Chuang,

Peng

et al. 2024

Clin Mol Hepatol

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Section: Discussionmentioning

confidence: 99%

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients

Yuen,

Chuang,

Peng

et al. 2024

Clin Mol Hepatol

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“…33 Addition of vebicorvir to GalNAc-siRNA (AB-729) plus NA did not result in greater decrease in HBsAg level compared to AB-729 and NA while addition of another CAM (JNJ-6379) to siRNA (JNJ-3989) and NA resulted in a smaller decrease in HBsAg level compared to siRNA and NA suggesting an antagonistic effect. 30 Preliminary data from a small trial of a second-generation CAM (ALG-00184) with or without entecavir showed HBsAg decrease by >1 log 10 in a few patients after 48 weeks treatment 34 providing hope that CAMs may have a role in HBV cure.…”

Section: Direct-acting Antivirals 1) Entry Inhibitorsmentioning

confidence: 99%

Toward a Functional Cure for Hepatitis B

Lok

2024

Gut and Liver

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Current treatment of chronic hepatitis B virus (HBV) infection, pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogue (NA), can suppress HBV replication, reverse liver inflammation and fibrosis, and decrease risks of cirrhosis and hepatocellular carcinoma, but hepatitis B surface antigen (HBsAg) loss is rare. Functional HBV cure is defined as undetectable HBsAg and unquantifiable serum HBV DNA for at least 24 weeks after a finite course of therapy. This requires suppression of HBV replication and viral protein production as well as restoration of immune response to HBV. Direct-acting antivirals targeting virus entry, capsid assembly, viral protein production and secretion are in clinical trials. In parallel, immune modulatory therapies to stimulate HBV-specific immune response and to remove immune blockade are being tested. Clinical trials of direct-acting antivirals alone or immune modulatory therapies alone have not been successful in achieving HBV cure. Recent combinations of direct-acting antivirals and immune modulatory therapies have shown promising results particularly with combinations that included pegIFN-α. These results need to be confirmed in larger studies with longer follow-up, and further work is needed to develop simpler regimens with fewer drugs that can be administered orally and safely. While there is a strong desire to develop finite therapies that can achieve HBV cure, safety is paramount and new therapies must provide incremental value compared to standard of care, which is predominantly long-term NA therapy.

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“…Some other promising CAM-Es molecules include ALG-000184, a potent inhibitor with successful phase 1 trials (NCT04536337) (92), Canocapavir (ZM-H1505R) that was well tolerated (Phase 1b, NCT05470829) (93), and GST-HG141 (phase 1, NCT04386915 & NCT04868981) (94). Many CAMs have been reported and are under investigation in clinical trials without their exact CAM phenotype described (Recently reviewed (28,55)).…”

Section: Class I: Cam-amentioning

confidence: 99%

Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure

McFadden

Sarafianos

2023

GHM

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Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.

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Safety, pharmacokinetics, and antiviral activity of the class II capsid assembly modulator ALG-000184 in subjects with chronic hepatitis B

Cited by 12 publications

References 0 publications

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients

Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients

Toward a Functional Cure for Hepatitis B

Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure

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