The development and treatment of chronic hepatitis B with the combination therapy of Roche CPAM and TLR7 agonist has been approved in China

Transferred from: Medical Mission Hills < br / > according to the information publicized by the drug evaluation center (CDE) of China National Drug Administration, Roche's ro7049389 tablets and ro7020531 tablets combined therapy have obtained a number of implied permits for clinical trials in ChinaThe indications are combined therapy for chronic hepatitis BRo7049389 is a kind of inhibitor of hepatitis B virus (HBV) capsid protein assembly, which can affect virus replication by inhibiting capsid protein assemblyRo7020531 is a toll like receptor 7 (TLR7) agonistAt present, the two drugs are in phase 2 clinical stage in the world< br / > chronic hepatitis B virus infection is a common cause of liver disease worldwide, especially in Southeast AsiaAccording to the World Health Organization (who), there are about 257 million HBV infected patients in the worldAt present, although vaccines and nucleoside / nucleotide analogues (NUC) have been able to reduce the rate of new infection and delay the progress of liver disease, the scientific and medical circles are not satisfied with the status quoThey have begun to work together to develop innovative antiviral drugs and immunotherapies aimed at curing this infection< br / > ro7049389 and ro7020531 are two innovative drugs developed by Roche to be used in the treatment of chronic hepatitis B< br / > HBV capsid is assembled by core proteinBefore retroviral, HBV reverse transcriptase and HBV pre genomic RNA (pgRNA) need to be properly wrapped by capsid proteinTherefore, blocking the assembly of capsid protein, or accelerating the degradation of capsid protein, will block the assembly process of capsid, thus affecting virus replicationIn addition, the 149 amino acid residues at the N- end of the core protein dimerization motif and assembly domain have no homologous sequence of human proteinTherefore, the inhibitor of capsid assembly is regarded as a new target of anti hepatitis B drug development< br / > ro7049389 is a kind of small molecule I HBV core protein allosteric modulator (CPAM) developed by RocheIt can inhibit HBV replication by inducing the formation of abnormal hepatitis B virus core aggregates, leading to defective capsid assembly, and may restore the host's immune response to HBV Ro7049389 can effectively inhibit HBV replication in vitro and in vivo animal models < br / > according to a phase 1 clinical data published by Roche at the 54th annual meeting of the European Society for liver research (EASL) in 2019, HBV DNA and RNA decreased significantly in all cohorts Ro7049389 showed good anti HBV activity 28 days after administration in patients with chronic HBV infection and good tolerance < br / > according to the Chinese drug clinical trial registration and information publicity platform, Roche has completed a randomized and open phase 1 clinical trial in healthy Chinese subjects to evaluate the safety and tolerance of ro7049389 single drug therapy compared with placebo after single and multiple oral dose increases In addition, ro7049389 is also carrying out a non randomized international multi center (including China) phase 2 clinic to evaluate the safety and effectiveness of ro7049389 in combination with NUC and PEG-IFN in patients with chronic hepatitis B < br / > ro7020531 is a dual prodrug of TLR7 agonist ro7011785 developed by Roche, which belongs to oral small molecular compound TLR7 activator can activate the activity of B and T cells and cytokines, and then enhance the host immune activity of human body to eliminate all hepatitis B virus < br / > ro7020531 can stimulate human peripheral blood mononuclear cells (PBMC) to induce IFN α and various cytokines and chemokines, such as TNF α, IL-6 and IP-10 Roche is currently developing the drug for the treatment of chronic hepatitis B < br / > previous studies showed that the anti HBV effect of ro7020531 in mice model was dose-dependent TLR7 agonists could significantly reduce the level of HBV DNA in serum and HBsAg in chronic hepatitis B At the 2019 APASL, Roche published the results of a phase 1 clinical study of ro7020531 in healthy Chinese volunteers The single dose of ro7020531 has good safety and tolerance in Chinese healthy volunteers, without serious adverse reactions < br / > at present, Roche is exploring the effect of the combination of ro7049389 and ro7020531 in the treatment of chronic hepatitis B According to the data released earlier by the company, in the mouse model of adeno-associated virus hepatitis B virus (aav-hbv), the combination of the two drugs in research has shown the characteristics of inhibiting the expression of HBV DNA and HBsAg, and in some animals, there are also hepatitis B surface antibody (anti HBS) Clinicaltrials.gov According to the information on the website, Roche is carrying out a phase 2 clinical study to evaluate the safety, tolerance and effectiveness of CPAM (ro7049389) + TLR7 agonist (ro7020531) + nucleoside (T) ide in the treatment of chronic hepatitis B patients with normal liver function and without obvious fibrosis / cirrhosis < br / > congratulations to Roche's CPAM (ro7049389) + TLR7 agonist (ro7020531) combination therapy, which has been approved in China We hope that these studies can be carried out smoothly and provide a new treatment option for chronic hepatitis B patients as soon as possible ▽