Benitec Biopharma recently announced that a single injection of its investigational drug BB-HB-331, a DNA-directed RNA interference (ddRNAi) therapy targeting the hepatitis B virus (HBV), displays a robust and durable suppression of HBV in vivo.
DNA-directed RNA interference is Benitec’s unique RNAi platform for silencing unwanted genes, with the potential to produce one-shot cures for a range of diseases. Sydney, Australia-based Benitec’s approach has distinct advantages over other methods of gene silencing, such as siRNA, anti-sense and zinc finger nucleases.
BB-HB-331 combines an AAV8 capsid and recombinant DNA designed to express three short hairpin RNAs (shRNA) targeting and inhibiting viral RNA expressed from three regions across various genotypes of HBV.
The in vivo trial investigated BB-HB-331’s activity in a mouse model, in which the liver cells were replaced with human hepatocytes, leaving the mouse prone to HBV infection. Once mice were infected with HBV, they received treatment with a single BB-HB-331 injection. During the 56-day study, serum antigen levels, HBV viral proteins, and extracellular HBV DNA were assessed every week.
The results revealed that a single injection of BB-HB-331 led to a reduction of HBV DNA serum levels by 1.83 logs, corresponding to a 98.5 percent elimination of circulating HBV. The results further revealed that a single treatment led to a 94.9 percent reduction in intracellular liver HBV DNA. It also suppressed serum antigens HBsAg and HBeAg by 97.6 percent and 92.6 percent, respectively. Moreover, it decreased the levels of HBV viral RNA and cccDNA.
This data validates previous BB-HB-331 in vitro results observed in human hepatocytes isolated from the same mouse model.
“These results demonstrate the utility of an approach that combines RNAi with gene therapy to treat HBV,” Benitec Chief Scientific Officer Dr. David Suhy said in a press release. “In addition to these encouraging results, we note that the HBV serum DNA and antigen levels continued to drop through the pre-determined conclusion of the study, and may not have reached their lowest levels. As previously communicated, Hep B represents a significant commercial opportunity and we will continue to apply key learnings from our clinical stage hepatitis C program to advance the Hep B program toward the clinic.”