Hope on the horizon: Emerging therapies for hepatitis D

Table 1 Diverse strategies target different stages of hepatitis D virus’s life cycle or indirectly disrupt hepatitis B virus processes essential for hepatitis D virus survival

Drug	Phase of development	Route of administration and dosage	Mode of action
Pegylated interferon alpha	Extensively studies	Subcutaneous. 180 µg weekly	Enhances immune response and reduces viral replication
Pegylated interferon lambda	Phase 2 & 3	Subcutaneous. 120 & 180 µg weekly	Targets type III interferon receptors on hepatocytes, activating immune responses specifically in the liver
Bulevirtide	Phase 3	Subcutaneous. 2 mg (approved) & 10 mg daily	Inhibits entry of HDV by blocking NTCP, a receptor for HBV/HDV entry into hepatocytes
Huahui HH003	Phase 2	Intravenous. 10 & 20 mg/kg every 2 weeks	A human monoclonal antibody targeting the preS1 domain of the large envelope protein of HBV and HDV, preventing the binding of preS1 to NTCP
Tobevibart	Phase 2 & 3	Subcutaneous. 300 mg every 4 weeks	A monoclonal antibody that binds the antigenic loop of HBsAg. The drug inhibits the entry of HBV and HDV into naïve hepatocytes and reduces circulating HBsAg
Lonafarnib	Phase 3	Oral 50 mg twice a day (when given with ritonavir)	Inhibits prenylation of the large delta antigen, essential for HDV assembly and viral replication
Nucleic acid polymers	Phase 2	Intravenous. 500 mg weekly for 15 weeks followed by 250 mg weekly (when combined with pegylated interferon)	Blocks HDV envelope formation by targeting HBsAg. Prevents secretion of HDV virions from infected cells
Small Interfering RNAs (JNJ-3989, Elebsiran)	Phase 2 & 3	Subcutaneous. Every 4 weeks. JNJ 100 mg, Elebsiran 200 mg	Silence HBV genomic RNA, reducing viral replication and protein production, indirectly affecting HDV by reducing the supply of HBV envelope proteins required for HDV virion assembly

HDV: Hepatitis D virus; HBV: Hepatitis B virus; HBsAg: HBV surface antigen; NTCP: Sodium taurocholate co-transporting peptide.