Hepatitis B virus therapy: What’s the future holding for us?

Table 1 A list of hepatitis B virus vaccines in development

Treatment	Undetectable HBV DNA inHBeAg positive patients	Anti-HBeAg serconversion in HBeAg positive patients	HBV DNA < 300/400 copies/mL in HBeAg negative patients
Pegylated interferon	25	30	63
Lamivudine	39	22	72
Adefovir	21	12	51
Entecavir	67	22	90
Telbivudine	60	26	88
Tenofovir disoproxil fumarate	74	21	91

HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen.

Table 2 A Lists of hepatitis B virus vaccines in development

Name of vaccine	Type	Developed by	Phase
Sci-B-Vac	Prophylactic 3rd generation vaccine	SciVac Ltd, Israel	Approved in Israel, Asia and Africa
HEPLISAV-B	Prophylactic vaccine	Dynvax Technologies Corporation, United States	Phase III
GS-4774	Therapeutic vaccine	Gilead Sciences, United States	Phase II
Hepsyn-B	Therapeutic vaccine	Immune Targeting Systems Ltd, United Kingdom	Pre-clinical
VAXINE’s HBV Vaccine	Therapeutic	Vaxine Pty, Ltd, Australia	Phase I
VAXINE’s HBV Vaccine	Prophylactic	Vaxine Pty, Ltd, Australia	Phase II
HBV+ DRibbles vaccine	Prophylactic and therapeutic	Southeast University, Nanjing, Jiangsu, China	Pre-clinical
ABX 203	Therapeutic	ABIVAX, France	Multicenter Phase II/III Trials
INO-1800	Therapeuti	Inovio Pharmaceuticals, United States and Roche	Phase I (expected to start in 2015)
DV-601	Therapeutic	Dynvax Technologies Corporation, United States	Phase Ib
Altravax Therapeutic Vaccine	Therapeutic	Altravax, Inc, United States	Pre-Clinical

HBV: Hepatitis B virus.

Table 3 Immunomodulators in pipeline for hepatitis B virus treatment

Immune enhancer	Function	Developer	Phase
CYT-107	Recombinant IL-7	Cytheris SA, France	Phase II
TG-1050	Adenovirus based targeted immunotherapy	Transgene SA, France	Pre-clinical
GS-9620	TLR-7 agonist	Gilead Sciences, United States	Phase II
GC1102	Monoclonal antibodyRecombinant HBIg	Green Cross Corporation, Japan	Phase II
CYT-003	TLR-9 agonist	Tekmira Pharmaceuticals Corporation, Canada	Pre-clinical (Phase II for Asthma)
SB 9200	RIG-I and NOD2 activator	Spring Bank Pharmaceuticals, United States	Phase II

HBV: Hepatitis B virus; HBIg: Hepatitis B Immunoglobulin; TLR: Toll-like receptor; RIG-I: Retinoic acid-inducible gene I; NOD2: Nucleotide-binding oligomerization domain containing 2; IL-7: Interleukin-7.

Table 4 Non-nucleoside anti-viral drugs in development for hepatitis B virus

Name	Mechanism	Developed By	Phase
CpAMs	Allosteric Modulation of HBCp	Assembly Biosciences, United States	Pre-clinical
AT61 and AT130	Assembly Activation (Inhibit Capsid Assembly)	Victorian Infectious Diseases Reference Laboratory, Australia	Pre-clinical
BAY41-4109	Assembly Activation (Inhibit Capsid Assembly)	AiCuris, Germany	Phase I
NVR 3-778	HBV Cp Inhibition (cccDNA suppression)	NoviraTheraputics, United States	Phase Ib
NVP018	Cyclophilin inhibition	Tekmira Pharmaceuticals Corporation, Canada	Phase I
TKM-HBV4G and TKM-HBV3G	RNAi	Tekmira Pharmaceuticals Corporation, Canada	Phase I
STING agonists	PRR Activation	Tekmira Pharmaceuticals Corporation, Canada	Pre-clinical
ARC-520	RNAi	Arrowhead Research Corporation, United States	Phase II
ALN-HBV	RNAi	Alnylam Pharmaceuticals, Inc. United States	Pre-clinical
GLS4	Assembly Activation (Inhibit Capsid Assembly)	HEC Pharm Group, China	Phase II (China)
BSBI-25	cccDNA Inhibition	Baruch S. Blumberg Institute, United States	Pre- clinical
Birinapant	SMAC	TetraLogic Pharmaceuticals, United States	Phase I
CPI-431-32	Inhibition of cyclophilin A	Ciclofilin Pharmaceuticals, United States	Pre-clinical
Myrcludex B	HBV entry inhibition	Hepatera Ltd, Russia and MYR GmbH, Germany	Phase II
Simvastatin	HMG CoA reductase inhibitor	University of Oklahoma and United States Veterans Administration	Phase I

RNAi: RNA inhibition; HBV Cp: Hepatitis B virus core protein; PRR: Pattern recognition receptors; SMAC: Synthetic small molecule and peptidomimetic of second mitochondrial-derived activator of caspases.

Table 5 Nucleoside analogs in development for hepatitis B virus

Name	MOA	Developed by	Phase
Clevudine	DNA polymerase inhibition	Bukwang Pharmaceutical, South Korea	Approved in South Korea and Philippines
Besifovir	DNA polymerase inhibition (pro-drug)	Ildong Pharmaceuticals and LG Life Sciences	Phase III
Tenofoviralafenamide	DNA polymerase inhibition (pro-drug)	Gilead Sciences, United States	Phase III
CMX157	DNA polymerase inhibition (pro-drug)	ContraVir Pharmaceuticals, United States	Phase III
AGX-1009	DNA polymerase inhibition (pro-drug)	Agenix, Australia	Phase I

HBV: Hepatitis B virus; MOA: Mechanism of action.