Breaking news: RNAi can significantly inhibit hepatitis B and is expected to become a new treatment for HBV

Recently, Dicerna Pharmaceuticals announced the latest results in the phase 1 clinical trial of RNAi therapy RG6346 (formerly known as DCR-HBVS), which was jointly developed by the company and Roche for the treatment of chronic hepatitis B virus (HBV) infection. The test results showed that once a month, a total of 4 RG6346 treatments resulted in a significant and lasting decrease in biomarkers of HBV disease activity. After the last administration, the level of hepatitis B surface antigen (HBsAg) continued to decline for up to 1 year.

About Hepatitis B Virus (HBV)

Hepatitis B virus (HBV) infection is the most common serious liver infection in the world. According to estimates by the World Health Organization (WHO), there are more than 292 million chronic hepatitis B patients worldwide. More than 800,000 patients die every year. HBV is also the main cause of liver cancer, and liver cancer is the second leading cause of cancer deaths in the world. Although existing treatments for hepatitis B can inhibit HBV replication, they rarely achieve long-term "functional cure" effects.

The reason why hepatitis B is difficult to cure is that HBV can produce covalently closed circular DNA (cccDNA) and integrated sequences in the nucleus of infected cells. The half-life of these sequences is very long, and current standard therapies (such as nucleotide (t)ide analogs) cannot effectively eliminate cccDNA.

Figure 1: The action of RG6346.

About RG6346

RG6346 is a chemically optimized double-stranded RNA that can effectively induce RNAi to selectively knockdown specific genes involved in the production of HBV messenger RNA (mRNA) and the virus entering liver cells.

By attaching N-acetylgalactosamine (GalNAc) sugars to one or more points of RG6346, a variety of effective and proprietary conjugate delivery configurations are produced. These molecules specifically bind to the highly expressed asialoglycoprotein (ASGPR) receptors on target cells, leading to internalization and entry into the cellular RNAi mechanism, thereby specifically reducing the production of HBV mRNA and genes required for HBV.

Figure 2: RG6346 is an S-targeting investigational synthetic dsRNAi therapeutic.

As Dr. Shreeram Aradhye, Executive Vice President and Chief Medical Officer of Dicerna said: "RNAi is a promising therapeutic model for inhibiting HBsAg, and it may provide a strong foundation for the functional treatment of chronic HBV infection."