Qilu Pharmaceutical introduced over 280 million US dollars! Hepatitis B RNAi therapy declares clinical application in China

Today (May 10), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that Arbutus Biopharma and Qilu Pharmaceutical jointly submitted a clinical trial application for AB-729 injection, which was accepted. According to public information, AB-729 is an RNAi drug developed by Arbutus for the treatment or prevention of hepatitis B. In December 2021, Qilu Pharma and Arbutus entered into an exclusive license agreement and strategic cooperation for the development and commercialization of the drug candidate in Greater China (including mainland China, Hong Kong, Macau and Taiwan), with down payment and milestones for this cooperation Payments up to $285 million.

Chronic hepatitis B is a potentially life-threatening infection of the liver caused by the chronic hepatitis B virus (HBV), which can lead to cirrhosis and liver cancer. The reason why chronic hepatitis B is difficult to cure is that in addition to the replication of HBV in the body, a large number of proteins produced by the virus will inhibit the immune response of the human body, resulting in the inability of immune cells to control the replication of the virus. Therefore, to reactivate the function of immune cells, it is necessary to reduce the expression of viral proteins.

RNA interference (RNAi) is a mechanism present in living cells that inhibits the expression of specific genes, thereby affecting the production of specific proteins. AB-729 is a hepatocyte-targeting RNAi drug that uses a novel covalently coupled N-acetylgalactosamine (GalNAc) delivery technology developed by Arbutus and can be administered subcutaneously. In preclinical models, AB-729 inhibits HBV viral replication, reduces all viral RNA transcript copies, and reduces all HBV antigens, including hepatitis B surface antigen (HBsAg), showing pan-genotypic activity across all HBV genotypes .
The effect of AB-729 against hepatitis B has been preliminarily verified in clinical studies. Arbutus announced the results of a study of AB-729 at the European Association for the Study of the Liver (EASL) International Liver Congress (ILC2021) in 2021. Data from this study showed that all dosing regimens resulted in a significant reduction in HBsAg in HBV-infected subjects who had previously received stable nucleoside (acid) analog therapy for at least 6 months, with 75% (15/20) of subjects HBsAg dropped below 100 IU/mL. At 20 weeks of dosing, subjects' HBsAg levels showed a sustained and stable plateau in all dosing regimens.

In addition, increased plasma interferon-γ (IFN-γ) levels, proliferation of HBV-specific T cells, or increased levels of IFN-γ expressed by HBV-specific T cells were observed in some subjects. Elevated levels of these biomarkers suggest that long-term suppression of HBsAg levels with AB-729 may re-awaken the human immune system's specific response to HBV.

It is hoped that the follow-up clinical research of AB-729, an RNAi drug, will proceed smoothly and bring new treatment options to patients as soon as possible.