Development of treatment for chronic hepatitis B Roche CpAM and TLR7 agonisant combination therapy approved clinical in China

Roche's RO7049389 tablets and RO7020531 combination therapies have been implicitly approved in a number of clinical trials in China, according to the China National Drug Administration's Drug Review Center (CDE), which is a combination of the treatment of chronic hepatitis BRO7049389 is a hepatitis B virus (HBV) shell protein assembly inhibitor that can affect virus replication by inhibiting shell protein assemblyRO7020531 is a toll-like receptor 7 (TLR7) agonisantCurrently, both drugs are in Phase 2 clinical phase son-in-practice worldwideChronic hepatitis B virus infection is a common cause of liver disease worldwide, particularly in Southeast AsiaThe World Health Organization (WHO) estimates that there are about 257 million HBV-infected people worldwideAt present, while vaccines, nucleotide/nucleotide analogues (NUC) etchave been able to reduce new infection rates and slow the progression of liver disease, the scientific and medical communities are not satisfied with the status quo and have begun to work together to develop innovative antiviral drugs and immunology therapies aimed at curing the infectionRO7049389 and RO7020531 are two innovative drugs developed by Roche for chronic hepatitis B curative treatmentRO7049389: The shell protein assembly inhibitor HBV shell is made of core protein assembly, and before reverse transcription, HBV reverse transcriptase, HBV pre-genome RNA (pgRNA) needs to be properly wrapped in shell proteinTherefore, blocking the garment shell protein assembly, or speeding up the degradation of shell protein, will block the shell assembly process, thus affecting virus replicationIn addition, the N-end 149 amino acid residues that make up the core protein dipolymerization base sequence and assembly structure domain do not have a homologous sequence of human proteinsTherefore, shell protein assembly inhibitors are regarded as a new target for the development of anti-hepatitis B drugsRO7049389 is a small molecule I HBV core protein alterent (CpAM) developed by RocheIt inhibits HBV replication by inducing the formation of the core aggregate of the abnormal hepatitis B virus, causing defective shell assembly, and possibly restoring the host's immune response to HBVIn vitro determination based on cell and in vivo animal models, RO7049389 can effectively inhibit HBV replicationAccording to a phase 1 clinical data presented by Roche at the 54th annual meeting of the European Society for The Study of The Liver (EASL) in 2019, all the queues showed a significant decrease in HBV DNA and RNA, and RO7049389 showed better anti-HBV activity and good tolerance 28 days after administering the drug in patients with chronic HBV infection According to the China Drug Clinical Trial Registration and Information Disclosure Platform, Roche has completed a random, open Phase 1 clinical trial among healthy Chinese subjects to assess the safety and tolerance of RO7049389 monodrug therapy compared to placebo after an increase in the dose of single and multiple oral administrations In addition, RO7049389 is conducting a non-randomized International Multicenter (including China) Phase 2 clinical program aimed at assessing the safety and efficacy of RO7049389 in combination with NUC and polyglycol interferon (PEG-IFN) in patients with chronic hepatitis B RO7020531: TLR7 agonising RO7020531 is a double precursor drug developed by Roche, TLR7 agonisant RO7011785, which belongs to oral small molecule compounds TLR7 agonists activate the body's B-cell and T-cell activity and cytokines, which in turn enhances the body's host immune activity to remove all hepatitis B virus from the body RO7020531 can stimulate the generation of peri-peripheral blood single nuclear cells (PBMC) by RO70111785, and various cytokines and chemofactors such as TNF alpha, IL-6, and IP-10 Roche is currently developing the drug for the treatment of chronic hepatitis B Previous studies have shown that THE anti-HBV effect of RO7020531 in mouse models shows drug dose dependence, and TLR7 agonists significantly reduce serum HBV DNA and chronic hepatitis B surface antigen levels (HBsAg) At the 2019 Asia Pacific Hepatology School Year (2019 APASL), Roche published the results of the first phase of clinical studies conducted by RO7020531 among healthy Chinese volunteers The study showed that a single dose of RO7020531 had good safety and tolerance in Healthy Volunteers in China, and no serious adverse reactions Currently, Roche is exploring the effects of the combination of RO7049389 and RO7020531 as it treats chronic hepatitis B According to the company's earlier release, in the adenovirus-hepatitis B virus (AAV-HBV) mouse model, the two drugs in combination drugs have been shown to inhibit the expression of HBV DNA and HBSAg, and in some animals also appeared in the surface antibodies of hepatitis B (anti-HBS) According to the Clinicaltrials.gov website, Roche is conducting a Phase 2 clinical study to assess the safety, tolerance and effectiveness of CpAM (RO7049389) and TLR7 agonists (RO7020531) and nucleoside (t)ide) combination therapy for patients with hepatitis B who have normal liver function and are free of apparent fibrosis/hepatic cirrhosis Congratulations to Roche CpAM (RO7049389) and TLR7 agonisant (RO7020531) joint therapy in China for its approval of clinical practice, and hope that these studies will proceed smoothly and provide a new treatment option for patients with chronic hepatitis B.