Early results of
hepatitis B virology showed that Pre-S1, a surface antigen, had a key amino acid sequence that mediated HBV infection in hepatocytes. According to the prevalent genotype HBV Pre-S1 in China, the R&D team of Hepper Pharmaceutical Industry designed the drug infrastructure of Heppler peptide. Its patent application was earlier than that of MycludexB, which originated from the amino acid sequence of C genotype HBV Pre-S1 in the world. It belongs to the new drug originally developed by the first-in-class inhibitor of HBV entry. Pre-clinical studies have shown that heptapeptide can bind to the surface of hepatocytes and block HBV infection in vivo and in vitro. Pre-clinical research and development of new drugs has been awarded "Major New Drug Creation" National Science and Technology Major Special Project, and submitted to CFDA for clinical trials in October 2012. In November 2012, NTCP, a sodium-cholic acid transporter protein, was identified as a receptor for HBV infection by Chinese scientist Dr. Li Wenhui. This achievement is a key milestone in the field of hepatitis B research. Heprapeptide was subsequently confirmed to bind specifically to NTCP, clarifying the exact mechanism of blocking HBV infection. In patients with chronic hepatitis B, hepatocytes infected by HBV are destroyed and cleared by the immune system. Newborn healthy hepatocytes are reinfected by the remaining HBV virus, forming a clearance-reinfection cycle. Existing nucleoside and interferon therapeutics only inhibit the replication of hepatocytes infected with HBV, lack of protection for healthy hepatocytes, and can not interrupt the cycle of clearance and reinfection, which may be one of the reasons for the lack of curative effect of existing hepatitis B therapeutics. Heprapeptide protects the newborn healthy hepatocytes by binding with NTCP, and HBV infected hepatocytes are gradually cleared by the immune system or drug treatment, which may eventually lead to the cure of hepatitis B. This product is expected to apply for new drug listing after completing phase III clinical research in 2022.
In 2018, NMPA took the lead in issuing the Guiding Principles for Clinical Trials of Antiviral Therapeutic Drugs for Chronic Hepatitis B (CHB) globally, which defined the end point of clinical research centered on sustained virological response and negative transformation of surface antigens, and provided timely standardization and guidance for clinical research and development of innovative drugs for hepatitis B. The determination of hepatitis B infection receptor NTCP has fundamentally promoted the deep understanding of the mechanism of hepatitis B infection and will make great contributions to the prevention and treatment of hepatitis B. With the development of clinical research and development of heptapeptide, the cure of hepatitis B is becoming more and more worthy of expectation.
