HBV is a DNA virus that infects the liver, and once infected, it is difficult to eliminate completely and is one of the major causes of liver diseases such as chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. Nucleic acid analog preparations, which are the current first-line drugs, strongly suppress HBV-DNA, which is the blueprint for HBV, but the therapeutic target for hepatitis B, HBs antigen (hepatitis B surface antigen), increases in blood levels. Achieving "functional cure," which refers to the disappearance of symptoms, is difficult with a single drug.

　This research team sought new therapeutic agents that effectively inhibit HBsAg and achieve functional cure, and found several drug candidates from among 3 types of compounds. Furthermore, after optimizing these drug candidates, we developed a new drug, SAG-524. This drug has a new mechanism of action that inhibits HBsAg and HBV replication by specifically destabilizing HBV-RNA and making it susceptible to degradation. It is possible to significantly reduce HBs antigen and HBV-DNA at very low concentrations.

Using hepatitis B model mice, we investigated the anti-HBV effect of the combination of SAG-524 and a nucleic acid analog preparation. As a result, HBV-DNA was further reduced than when administering a nucleic acid analog preparation alone, and HBs antigen was also reduced. was confirmed. Furthermore, in safety tests using mice and monkeys, no obvious toxicity was observed even when SAG-524 was administered at extremely high doses (1000mg/kg/day).

　SAG-524 can be administered orally, and additive effects have been confirmed in combination therapy with conventional nucleic acid analog preparations, so it is expected to be a new treatment option aimed at functionally curing hepatitis B. Preparations for clinical trials are currently underway.

Paper information:【Journal of Gastroenterology】A novel, small anti-HBV compound reduces HBsAg and HBV-DNA by destabilizing HBV-RNA