MedivirAB, a research based specialty pharmaceutical company focused on infectious diseases has started dosing and screening patients in two new phase III clinical trials, HPC3001 and HPC3011, respectively for its oral, once daily investigational protease inhibitor TMC435, developed by Janssen Pharmaceuticals for the treatment of Hepatitis C virus (HCV).

HPC3001 is a phase III efficacy, safety and tolerability study comparing TMC435 versus telaprevir, each in combination with Pegylated Interferon a-2a (PegINF) and ribavirin (RBV), in hepatitis C genotype-1 infected patients who were null or partial responders to prior PegINF/RBV therapy. The study which is a randomized, double-blind, double-dummy, two-arm study is targeted to enroll 744 patients.

The aim of the study is to demonstrate the efficacy of TMC435 based therapy compared to the approved telaprevir regimen in this difficult to treat population.

Patients will receive TMC435 150 mg once daily or telaprevir 750 mg administered every eight hours (q8h) in combination with PegINF/RBV for 12 weeks followed by 36 weeks of PegIFN/RBV alone. The primary endpoint of the study is sustained virological response at 12 weeks (SVR12).

HPC3011 is an open label, single arm phase III trial to explore the efficacy, safety and tolerability of TMC435 150 mg once daily, in combination with PegIFN/RBV in 100 treatment naïve or treatment experienced, Hepatitis C genotype-4 infected patients.

Current standard of care treatment for chronic HCV genotype-4 infection consists of 48 weeks of PegIFN/RBV with a large proportion of patients do not achieve SVR with this treatment regimen.

All subjects will receive 12 weeks triple therapy of TMC435 150 mg once daily and PegIFN/RBV, followed by PegIFN/RBV alone. The duration of total treatment is response guided in treatment naïve and prior relapser subjects and patients are eligible to stop all treatment at week 24 if predefined response-guided criteria are met. Subjects with cirrhosis will receive 48 weeks of therapy, irrespective of on-treatment virologic response and treatment history. The primary endpoint in the study is SVR12.

TMC435 - Ongoing global phase III program in brief:

TMC435-C208 or QUEST-1 in 375 treatment-naïve genotype-1 patients.

TMC435-C216 or QUEST-2 in 375 treatment-naïve genotype-1 patients.

TMC435-C3007 or PROMISE in 375 genotype-1 patients who have relapsed after prior interferon-based treatment.

Phase III programme in Japan, includes 417 genotype-1 treatment naïve and treatment experienced patients.

Charlotte Edenius, executive VP Research and Development, of Medivir commented, “We are extremely pleased to expand the phase III programme with these two new trials as we continue development of TMC435 for broad patient populations. The 744 patient HPC3001 study is aimed at further confirming the positive findings of the ASPIRE phase IIb trial in genotype-1 non-responder patient populations and in the HPC3011 study, the genotype-4 activity of TMC435 is being investigated.”

TMC435 is an investigational HCV protease inhibitor in late phase III clinical development. It is an efficacious, safe and well-tolerated once-daily (q.d.) drug jointly developed by Janssen Pharmaceuticals to treat chronic hepatitis C virus infections.

TMC435 is in phase III clinical development in combination with PegIFN/RBV but is also being evaluated with Direct-acting Antiviral (DAA) agents in interferon-free combinations both with and without ribavirin (RBV).

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3 per cent of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.