A phase 2a study evaluating the multi-dose activity of ARB-1467 in HBeAg positive and negative virally suppressed subjects with hepatitis B

Streinu-Cercel, Adrian; Gane, Edward; Cheng, Wendy; Sievert, William; Roberts, Stuart; Ahn, Sang Hoon; Kim, Y.J.; Agarwal, Kosh; Niforos, D.; Symonds, B.; Méndez, Patricia

doi:10.1016/s0168-8278(17)31850-0

Cited by 27 publications

(13 citation statements)

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“…ARB-1467 (NCT02631096) is a lipid nanoparticle (LNP) compound containing three siRNAs which target three distinct sites for post-transcriptional HBV gene suppression, including HBsAg. HBsAg reductions were achieved following single and multiple dose administration [ 47 ]. More results concerning this compound are eagerly awaited.…”

Section: Direct Acting Antiviralsmentioning

confidence: 99%

New Approaches to the Treatment of Chronic Hepatitis B

Alexopoulou

Vasilieva

Karayiannis

2020

JCM

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The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg loss, inhibition of new hepatocyte infection, elimination of the covalently closed circular DNA (cccDNA) pool, and restoration of immune function in order to achieve virus control. This review concentrates on new antiviral drugs that target different stages of the HBV life cycle (direct acting antivirals) and others that enhance both innate and adaptive immunity against HBV (immunotherapy). Drugs that block HBV hepatocyte entry, compounds that silence or deplete the cccDNA pool, others that affect core assembly, agents that degrade RNase-H, interfering RNA molecules, and nucleic acid polymers are likely interventions in the viral life cycle. In the immunotherapy category, molecules that activate the innate immune response such as Toll-like-receptors, Retinoic acid Inducible Gene-1 (RIG-1) and stimulator of interferon genes (STING) agonists or checkpoint inhibitors, and modulation of the adaptive immunity by therapeutic vaccines, vector-based vaccines, or adoptive transfer of genetically-engineered T cells aim towards the restoration of T cell function. Future therapeutic trends would likely be a combination of one or more of the aforementioned drugs that target the viral life cycle and at least one immunomodulator.

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Section: Direct Acting Antiviralsmentioning

confidence: 99%

New Approaches to the Treatment of Chronic Hepatitis B

Alexopoulou

Vasilieva

Karayiannis

2020

JCM

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“…These proteins are generated from both cccDNA and integrated DNA, including the surface antigen (HBsAg). The safety and efficacy of ARB-1467 was evaluated in a recent study over a period of 12 weeks in 24 subjects and showed declines in HBsAg levels with single and multiple doses [ 86 ]. BB-103 is a recombinant AAV8 vector which is designed to treat chronic HBV infection using RNAi, and targets three sequences in the Core, S-antigen and X protein regions on the HBV viral RNA.…”

Section: New Nasmentioning

confidence: 99%

Section: New Nasmentioning

confidence: 99%

Upcoming pharmacological developments in chronic hepatitis B: can we glimpse a cure on the horizon?

et al. 2017

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BackgroundHepatitis B virus (HBV) chronic infection affects up to 240 million people in the world and it is a common cause of cirrhosis and hepatocellular carcinoma (HCC). HBV covalently closed circular DNA (cccDNA) plays an essential role in HBV persistence and replication. Current pharmacological treatment with nucleos(t)ide analogues (NA) may suppress HBV replication with little or no impact on cccDNA, hence lifelong treatment is required in the vast majority of patients. Clearances of intrahepatic cccDNA and/or HBsAg are critical endpoints for future antiviral therapy in chronic HBV. Recent promising developments targeting different molecular HBV life cycle steps are being pre-clinically tested or have moved forward in early clinical trials.MethodsWe review the current state of the art of these pharmacological developments, mainly focusing on efficacy and safety results, which are expected to lay the ground for future HBV eradication. An inclusive literature search on new treatments of HBV using the following electronic databases: Pubmed/MEDLINE, AMED, CINAHL and the Cochrane Central Register of Controlled Trials. Full-text manuscripts and abstracts published over the last 12 years, from 2005 to March 2011 were reviewed for relevance and reference lists were crosschecked for additional applicable studies regarding new HBV antiviral treatment.ResultsHBV entry inhibitors, HBV core inhibitors, HBV cccDNA transcripts RNA interference, HBV cell apoptosis inducers, HBV RNA, viral proteins and DNA knock down agents, HBV release inhibitors, anti-sense nucleosides, exogenous interferon stimulation, interferon response stimulation and HBV therapeutic vaccines were reviewed.ConclusionThis review will provide readers with an updated vision of current and foreseeable therapeutic developments in chronic hepatitis B.

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“…As a result, tumor reduction was achieved, but some serious AEs (SAEs) were also observed. 150 Moreover, several other RNAi therapeutics also employ liposomes as delivery materials, e.g., ALN-VSP, 151 ALN-PCS, 152 MRX34, 183 Atu027, 175,184 ARB-1467, 185 ARB-1740, 186,187 etc. The clinical studies of all these therapeutics are currently discontinued.…”

Section: Sirna Modificationmentioning

confidence: 99%

Therapeutic siRNA: state of the art

Zhong

Weng

et al. 2020

Sig Transduct Target Ther

887

705

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RNA interference (RNAi) is an ancient biological mechanism used to defend against external invasion. It theoretically can silence any disease-related genes in a sequence-specific manner, making small interfering RNA (siRNA) a promising therapeutic modality. After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO ® (patisiran) and GIVLAARI™ (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-term pharmaceutical history of human beings, siRNA therapy currently has set up an extraordinary milestone, as it has already changed and will continue to change the treatment and management of human diseases. It can be administered quarterly, even twice-yearly, to achieve therapeutic effects, which is not the case for small molecules and antibodies. The drug development process was extremely hard, aiming to surmount complex obstacles, such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity, stability, specificity and potential off-target effects. In this review, the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed. All clinically explored and commercialized siRNA delivery platforms, including the GalNAc (N-acetylgalactosamine)-siRNA conjugate, and their fundamental design principles are thoroughly discussed. The latest progress in siRNA therapeutic development is also summarized. This review provides a comprehensive view and roadmap for general readers working in the field.

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A phase 2a study evaluating the multi-dose activity of ARB-1467 in HBeAg positive and negative virally suppressed subjects with hepatitis B

Cited by 27 publications

References 0 publications

New Approaches to the Treatment of Chronic Hepatitis B

New Approaches to the Treatment of Chronic Hepatitis B

Upcoming pharmacological developments in chronic hepatitis B: can we glimpse a cure on the horizon?

Therapeutic siRNA: state of the art

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