Bulevirtide for treating chronic hepatitis D

Bulevirtide for treating chronic hepatitis D

• sodium taurocholate co-transporting polypeptide (NTCP) is the cell surface receptor for HBV and HDV entry into hepatocytes (1)
  • bulevirtide (BLV) interferes with the binding of NTCP and HBV/HDV
    • BLV is a large polypeptide mimics a region of the pre-S1 HBsAg and blocks viral entry by inhibitory competition
      • is a synthetic N-acylated pre-S1 lipopeptide that blocks the binding of HBsAg-enveloped particles to NTCP, which is the cell entry receptor for both HBV and HDV (2)
      • prevents the entry of HDV into hepatocytes, thereby decreasing the number of HDV-RNA templates needed for the synthesis of L- and S-HDAg
      • since there is no stable reservoir for HDV-RNA within infected hepatocytes, viral clearance might be achieved using antivirals for a minimum timeframe (1)
    • BLV is administered subcutaneously once daily at doses between 2 and 10 mg

NICE state:

• bulevirtide is recommended as an option for treating chronic hepatitis D in adults with compensated liver disease only if:
  • there is evidence of significant fibrosis (METAVIR stage F2 or above or Ishak stage 3 or above) and
  • their hepatitis has not responded to peginterferon alfa-2a (PEG-IFN) or they cannot have interferon-based therapy
  • bulevirtide is only recommended if the company provides it according to the commercial agreement
• the NICE committee stated "..clinical trial evidence shows that bulevirtide is effective compared with standard care despite some uncertainties around how long it works for.."

Notes:

• hepatitis D virus (HDV; Delta virus, family: Komlioviridae) depends on hepatitis B virus (HBV) envelope (HBV surface antigen, HBsAg) to form infectious HDV particle
  • HDV infection frequently causes progression to cirrhosis and hepatocellular carcinoma (HCC) (2)

Reference

• Soriano V et al. Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy. Drug Des Devel Ther. 2023 Jan 21;17:155-166. doi: 10.2147/DDDT.S379964. PMID: 36712949; PMCID: PMC9875571.
• Ferenci P, Reiberger T, Jachs M. Treatment of Chronic Hepatitis D with Bulevirtide-A Fight against Two Foes-An Update. Cells. 2022 Nov 8;11(22):3531. doi: 10.3390/cells11223531. PMID: 36428959; PMCID: PMC9688382.
• NICE (June 2023). Bulevirtide for treating chronic hepatitis D