The potential to treat HBV
RG6346 is an investigational GalXC RNAi therapy in development with Roche for the treatment of chronic hepatitis B virus (HBV) infection Chronic HBV increases the risk of developing liver failure, liver cancer or cirrhosis – a condition that permanently scars the liver. RG6346 has the potential to contribute to the ultimate goal of achieving a functional cure in patients with chronic HBV and is currently being studied by Roche as part of a Phase 2 clinical trial in combination with other treatment regimens to induce functional cures in patients.
RG6346 is designed to knock down selectively viral hepatitis B surface antigen (HBsAg) messenger RNA (mRNA) and protein expression in liver hepatocytes. HBsAg is required for the HBV virus lifecycle and is a marker used to determine the extent of chronic HBV viral activity. Preclinical data have demonstrated greater than 99.9% reduction in circulating HBsAg in mouse models of HBV infection. Results from a Phase 1 trial of RG6346 demonstrated that four monthly doses of RG6346 treatment resulted in substantial and durable reductions in HBsAg levels lasting up to one year following the last dose.
RG6346 clinical trials
In October 2019, Dicerna entered into a research collaboration and licensing agreement with Roche to develop RG6346 for the treatment of patients with non-cirrhotic chronic HBV. Dicerna initiated evaluation of RG6346 in a Phase 1 randomized, placebo-controlled study designed to evaluate the safety and tolerability of RG6346 in healthy volunteers and in patients with non-cirrhotic chronic HBV. Positive initial results from this trial were presented in November 2020 at the American Association for the Study of Liver Diseases (AASLD): The Liver Meeting® Digital Experience 2020™.
Roche is responsible for post-Phase 1 clinical development and in March 2021 initiated RG6346 in a Phase 2 combination clinical trial that is designed to evaluate RG6346 alone and in combination with other investigational agents and approved chronic HBV treatments with different mechanisms of action.