Breakthroughs and challenges in the management of pediatric viral hepatitis

Table 5 Investigational drugs for chronic hepatitis B infection

Class	Compound	Mechanism	Known side effects	Route	Status	Ref.
Entry inhibitors	Bulevirtide	Blocks entry via interaction with NTCP	Injection site reactions, cholestasis	Subcutaneous (iv)	Approved for CHD (HBV/HDV) Phase II for HBeAg-CHB	European Association for the Study of the Liver[117] and Bogomolov et al[118]
Capsid assembly modulators	JNJ-56136379	Prevents encapsidation of pgRNA Prevents formation of cccDNA	Hypertransaminasemia	Oral	Phase II for CHB ± NA	Zoulim et al[105]
Capsid assembly modulators	ABI-H0731 (Vebicorvir)	Prevents packaging of pgRNA into capsids	Skin rash, dizziness	Oral	Phase II for CHB ± NA	Yuen et al[106]
HBsAg secretion inhibitors	REP-2139	Inhibits the secretion of HBsAg subviral particles	Fever, chills, hypertransaminasemia, leukopenia	iv	Phase II for CHB + NA Phase II for CHD + peg-IFN-α	Bazinet et al[109,110]
HBsAg secretion inhibitors	REP-2165	Inhibits the secretion of HBsAg subviral particles	Fever, chills, hypertransaminasemia, leukopenia	iv	Phase II for CHD + peg-IFN-α	Bazinet et al[110]
RNA interference	JNJ-3989	Silences the mRNA viral transcripts reducing HBsAg	-	iv	Phase II for CHB	Yuen et al[111] and Gane et al[112]
RNA interference	VIR-2218	Silences the mRNA viral transcripts reducing HBsAg	-	iv	Phase II for CHB	VIR Biotechnology[113]
RIG-1 agonist	Inarigivir (SB9200)	Activates PRR RIG-1 and IFN-I response	Headache, dizziness, UTI, ILI, GI symptoms, hypertransaminasemia	Oral	Phase II for CHB + NA	Yuen et al[114]
Immune modifier	Selgantolimod (GS-9688)	TLR8 agonist	Nausea, vomiting, chills, headache, UTI	Oral	Phase II for CHB + NA	Gane et al[116]

CHB: Chronic hepatitis B; CHD: Chronic hepatitis D; GI: Gastrointestinal.; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; ILI: Influenza-like illness; NA: Nucleotide analogue; peg-IFN-: Pegylated interferon α; UTI: Urinary tract infection.