Hepatitis C is a result of a hepatocyte specific infection induced by the virus known as HCV. Chronic HCV may lead to significant liver disease, including chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. According to the World Health Organization, up to 170 million people are chronically infected with HCV worldwide, and more than 350,000 people die from HCV annually. The CDC estimates that there are currently approximately 3.2 million persons infected with HCV in the United States. Regulus believes that its’ miR-122 antagonist, RG-101, may be a useful agent in emerging combination regimens to address difficult-to-treat genotypes and to potentially expand upon the current therapies available to clinicians treating HCV patients.
RG-101 is Regulus’ wholly-owned, GalNAc-conjugated anti-miR targeting miR-122, currently in Phase II testing for the treatment of HCV. In a completed Phase I clinical study, Regulus demonstrated that treatment with a single subcutaneous dose of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy resulted in significant and sustained viral load reductions in all treated HCV patients, including patients with difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen. To date, RG-101 has a favorable safety profile with no serious adverse events or discontinuations reported in the treated HCV patients.
In early August 2015, Regulus announced that it initiated a Phase II study evaluating the efficacy of RG-101 when given in combination with marketed anti-HCV agents Harvoni®, Olysio®, and Daklinza™ for 28 days. Regulus expects to report interim data from this Phase II study in early Q1 2016 and sustained viral response data 12 weeks following conclusion of treatment (SVR12) in the second quarter of 2016.
In early November, Regulus announced that the company entered into a clinical trial collaboration agreement with GlaxoSmithKline (“GSK”) evaluate an HCV combination regimen. In the first quarter of 2016, Regulus plans to initiate a Phase II study evaluating the combination of RG-101 and GSK2878175, a non-nucleoside NS5B polymerase inhibitor, in treatment-naïve patients chronically infected with HCV genotypes 1 and 3. Concurrently, GSK will work on developing a long-acting parenteral formulation for injection (“LAP”) of GSK2878175 which could improve patient compliance through reduced dosing intervals and potentially extend opportunities for HCV therapeutic intervention. This LAP formulation of GSK2878175 may be used in additional clinical trials together with RG-101 following completion of the planned Phase II study, although any additional studies are not covered by the collaboration agreement.