Table 4.
Direct and Indirect Antiviral Agents Currently in Development
| Target | Mechanism of Action | Agent in Development | Current Stage of Development |
|---|---|---|---|
| Direct | |||
| Viral Entry | Blockage of the NTCP receptor | Bulevirtide | Phase 3* |
| Hepalatide | Phase 2 | ||
| Monoclonal antibody against the pre-S1 domain | VIR-3434 | Phase 1 | |
| Viral Transcription | mRNA disruption by siRNA | JNJ-3989 | Phase 2 |
| AB-729 | Phase 2 | ||
| RG6346 | Phase 2 | ||
| VIR-2218 | Phase 2 | ||
| ALG-125755 | Phase 1 | ||
| BB-103 | Pre-Clinical | ||
| mRNA disruption by ASO | Bepirovirsen | Phase 2 | |
| IONIS-HBVLRx | Phase 2 | ||
| Core Protein | Capsid Inhibitor | EDP-514 | Phase 2 |
| Morphothiadin | Phase 2 | ||
| RG7907 | Phase 2 | ||
| Vebicorvir | Phase 2 | ||
| JNJ 56136379 | Phase 2 | ||
| ABI-H3733 | Phase 1 | ||
| AB-836 | Phase 1 | ||
| ALG-000184 | Phase 1 | ||
| QL-007 | Phase 1 | ||
| VNRX-9945 | Phase 1 | ||
| ZM-H1505R | Phase 1 | ||
| GLP-26 | Pre-Clinical | ||
| ABI-4334 | Pre-Clinical | ||
| cccDNA | Reducing HBX expression | Pevonedistat | Pre-Clinical |
| Dicoumarol | Pre-Clinical | ||
| HBV polymerase | Prodrugs of nucleotide analogues | Pradefovir | Phase 3 |
| HS-10234 | Phase 3 | ||
| NCO-48 fumarate | Phase 1 | ||
| Non-chain terminating nucleotide analogue | AT-2173 | Phase 2 | |
| HBsAg release | Nucleic Acid Polymers (NAPs) | REP 2139/2165 | Phase 2 |
| S-Antigen Transport-inhibiting Oligonucleotide Polymer (STOPS) | ALG-010133 | Discontinued | |
| Indirect | |||
| Innate immunity | TLR 7 agonist | Vesatolimod | Phase 2 |
| RG7854 | Phase 1 | ||
| TLR 8 agonist | GS-9688 | Phase 2 | |
| SBT 8230 | Preclinical | ||
| Adaptive immunity | Checkpoint inhibitor | Nivolumab | Phase 2 |
| Envafolimbab (ASC22) | Phase 2 | ||
| Immune Mobilizing Monoclonal T-cell Receptors Against Virus (ImmTAV) | IMC-I109V | Phase 1/2 | |
| Therapeutic vaccines | DNA vaccines | GS-4774 | Phase 2 |
| HB-110 | Phase 1 | ||
| INO-1800/9112 | Phase 1 | ||
| JNJ-64300535 | Phase 1 | ||
| MVA-HBV (VTP-300) | Phase 1 | ||
| TG1050 | Phase 1 | ||
| VRON-0200 | Preclinical | ||
| T-cell or B-cell epitope vaccine | εPA-44 | Phase 3 | |
| FP-02.2 (HepTcell) | Phase 2 | ||
| HBV envelope antigen vaccines | NASVAC | Phase 4 | |
| BRII-179 | Phase 2 | ||
| VVX001 | Phase 2 |
NTCP, sodium taurocholate co-transporting polypeptide; HBX, HBV X protein; HBsAg, HBV surface antigen; cccDNA, covalently closed circular DNA; siRNA, small interfering RNAs; ASO, antisense oligonucleotides.
*
For HBV/HDV co-infection not HBV monotherapy.