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

BMC Gastroenterology

Table 1 Novel agents against HBV and phase of development

Mode of action	Target	Drug	Clinical phase
Direct acting antivirals
Polymerase inhibition	HBV polymerase	Tenofovir alafenamide	Phase 3
Polymerase inhibition	HBV polymerase	Besifovir	Phase 3
Entry inhibition	NTCP	Myrcludex-B	Phase 2a
Core inhibitors	Nucleocapsid assembly	NVR 3–778	Phase 2
Core inhibitors	Nucleocapsid assembly	AT-61, AT130, Bay 41–4109	Preclinical
Cleavage of DNA	ccc-DNA	ZFNs,TALENs,CRISPR/Cas	Preclinical
Inhibition of ccc-DNA formation		CCC-0975 and CCC-0346	Preclinical
Non-cytolitic cccDNA degradation by inducing APOBEC3A and APOBEC3B		Lymphotoxin-b receptor agonist	Preclinical
Apoptosis induction by inhibiting cIAPs	CIAPs	Birinapant	Phase 1
Knock down HBV RNA, viral proteins and HBV DNA	HBV RNA	ARC-520, ARC-521	Phase 2
Block release of HBsAg	HBV RNA	REP-2139	Phase 2
Antisense nucleotides	Target RNA	ASOs	Preclinical
Host targeting agents
Exogenous interferon stimulation	Innate immunity TLR7	Toll-like receptor (TLR) agonist (GS-9620)	Phase 2
Stimulate IFN response	Innate immunity RIG-I	SB 9200	Phase 2
Therapeutic vaccination	Adaptive immunity	GS-4774 (Tarmogen)	Phase 2b
Therapeutic vaccination	Adaptive immunity	ABX203	Phase 2b

APOBEC apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3A and 3B, ASO antisense nucleotides, cccDNA covalently closed circular DNA, CIAPs Cellular inhibitor of apoptosis proteins, CRISPR/Cas clustered regulatory interspaced short palindromic repeats (CRISPR) and CRISPR associated (Cas) systems, NTCP sodium taurocholate co-transporting polypeptide, RIG-I Retinoic acid-inducible gene, TALENs transcription activator-like effector nucleases, ZFNs zinc-finger nucleases

ISSN: 1471-230X