Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents

Table 1 Novel therapeutic agents for treatment of chronic hepatitis B infection in phase II or III development

Drug name (therapeutic class)	Drug sponsor	Phase
Core/capsid inhibitors
JNJ56136379 (JNJ-6379)	Janssen Pharmaceutics	II
ABI-H0731 (Vebicorvir)	Assembly Biosciences	II
Entry inhibitors
Bulevirtide (Hepcludex, formerly Myrcludex)	Gilead Sciences	III
Small interfering RNA
GSK3228836 (Bepirovirsen)	Ionis Pharmaceuticals	III
VIR-2218	Vir Biotechnology	II
VIR-3314	Vir Biotechnology	II
JNJ-73753989 (JNJ-3989, formerly ARO-HBV)	GlaxoSmithKline Pharmaceuticals	II
Arbutus-729 (AB-729 or Imdusiran)	Arbutus Biopharma	II
HBsAg inhibition
REP 2139/REP 2165	Replicor	II
Toll-like receptor agonists
GS-9620 (Vesatolimod)	Gilead Sciences	II
GS-9688 (Selgantolimod)	Gilead Sciences	II
Therapeutic vaccines
GS-4774	Gilead Sciences	II
BRII-179	Brii Biosciences	II

Table 2 Summary of novel investigational agents in phase II trials for treatment of chronic hepatitis B infection

Drug name (therapeutic class)	Drug sponsor	Phase	Trial ID	Study design	Study population	Sample size	Intervention and control	Primary outcome
RG6346 (siRNA); RO7020531 (TLR-7 agonist)	Hoffman-La Roche	II	NCT04225715	Randomized, open-label, parallel assignment	Chronic HBV infection patients on established NA monotherapy for ≥ 12 months, HBV DNA < 20 IU/mL, ALT ≤ 1.5 ULN	280	Control arm: NA; Experimental arms: (1) CpAM (RO7049389) + TLR-7 agonist (RO7020531) + NA; (2) siRNA (RG6346) + NA; (3) siRNA (RG6346) + PEG-IFN + NA; (4) siRNA (RG6346) + TLR (RO7020531) + NA; (5) siRNA (RG6346) + PD-L1 LNA (R07191863) + NA	Percentage of participants with HBsAg loss at 24 wk after end of treatment
GC1102 (HBsAg neutralizing antibody)	Green Cross Corporation	II	NCT03801798	Double-blind, randomized, placebo-controlled, parallel-group	Chronic HBV infection patients on NA ≥ 24 wk before screening	42	Control arm: NA + placebo; Experimental arm: NA + GC1102	Proportion of participants with ≥ 1 log IU/mL reduction in HBsAg titer

CpAM: Core Protein Allosteric Modulator; HBV: Hepatitis B Virus; HBsAg: Hepatitis B surface antigen; LLOQ: Lower limit of quantification; NA: Nucleos(t)ide therapy; TLR: Toll-like receptor; SiRNA: Short interfering RNA; ULN: Upper limit of normal.