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 for the treatment of HCV. Regulus is currently evaluating RG-101 in an ongoing study being conducted in the Netherlands. The study has the following four parts: (I) a single ascending-dose study in which healthy volunteer subjects receive a single subcutaneous dose of RG-101, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg and 8 mg/kg or placebo; (II) a multiple-ascending dose study in which healthy volunteer subjects receive a monthly single subcutaneous dose for four months of RG-101 or placebo; (III) a single-dose drug-drug interaction study in which healthy volunteer subjects receive a single subcutaneous dose of RG-101 in combination with simeprevir, an approved DAA; and (IV) a single-dose study in which HCV patients receive either a single subcutaneous dose of RG-101 or placebo at two doses, 2 mg/kg of RG-101 (the first dose cohort) or 4 mg/kg of RG-101 (the second dose cohort), to assess the safety and viral load reduction. The primary objective is to evaluate safety and tolerability and the secondary objectives are to evaluate pharmacokinetics, viral load reduction and any impact an oral DAA, such as simeprevir, may have on the pharmacokinetics of RG-101. Up to 100 healthy volunteer subjects and HCV patients with multiple HCV genotypes and treatment history are planned to be enrolled.
In October 2014, Regulus demonstrated human proof-of-concept with RG-101 in HCV patients. Regulus reported interim results from the ongoing study demonstrating that treatment with a single subcutaneous dose of 2 mg/kg of RG-101 as monotherapy resulted in significant and sustained reductions in HCV RNA in a varied group of patients, including difficult to treat genotypes and patients who experienced viral relapse after a prior IFN-containing regimen. Additionally, RG-101 was safe and well tolerated and has demonstrated a very favorable pharmacokinetic profile to date, which Regulus believes may allow for combination with oral direct-acting antiviral agents to treat HCV.
Under its ‘Clinical Map Initiative’, Regulus has accelerated development of RG-101 and is pursuing a Phase II dual-track development strategy (i) to investigate RG-101 in combination with oral agents to potentially shorten treatment durations, optimize clinical outcomes and potentially improve responses in certain underserved HCV patient populations; and (ii) to investigate RG-101 further as a single agent to determine whether HCV viral cures are achievable with monotherapy treatment (single or multiple doses of RG-101). Regulus expects to initiate the above described studies in Europe and the United States in the second quarter of 2015, and expects to report viral load reduction and safety data from these studies in the fourth quarter of 2015.