| It is estimated that 296 million individuals had HBV infections. Current nucleos(t)ide or interferon treatment can suppress HBV-DNA replication in most patients but rarely is accompanied by a functional cure (HBsAg loss). Since cure therapy is not available, regimens with oral antiviral therapy followed by an add-on/switching to pegylated-interferon have been explored to enhance the frequency of functional cures. However, these approaches are only applicable to patients with low levels of HBsAg titers (<1500 U/mL) after receiving years of oral antiviral therapy. Recently, a broad spectrum of therapeutic molecules with antiviral effects that block the HBV life cycle at different steps is under clinical development to achieve a functional cure, which includes HBV entry receptor inhibitors, cccDNA disrupters, RNA silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors, and secretion inhibitors. Several compounds exhibit high antiviral potency either use alone or in combination with other regimens. In addition, new immune modulators have been investigated. Combination regimens using new antiviral therapies with immune modulators are expected to achieve better benefits and durability after the cession of the treatment. Several drugs in more advanced stages of clinical development (phase IIb or III) have resulted in HBsAg loss in a significant proportion of patients, which included bulevirtide, the siRNA VIR-2218, siRNA JNJ-73763989, monoclonal antibody VIR-3434, and capsid assembly modulator JNJ-56136379 (bersacapavir), and bepirovirsen (antisense oligonucleotide that targets HBV mRNA). The advances in HBV therapeutics will be discussed. |
