Therapeutic Safety and Efficacy of REP 9AC (REP 2055) in HBV or HCV Infected Patients

Chronic hepatitis B and C are long term conditions caused by infection of the body with the hepatitis B (HBV) and C (HCV) viruses. These infections often result in inflammation or scarring of the liver and can eventually lead to liver cirrhosis and liver failure. These infections are also one of the major causes of the development of hepatocellular carcinoma (liver cancer).

Although some drugs have been approved to treat chronic hepatitis B infections, they do not provide a complete cure except in rare cases (a cure generally means that a person loses the hepatitis B virus and develops protective surface antibodies). However, these drugs significantly decrease the risk of liver damage from the infection by slowing or stopping the virus from reproducing. Amongst the problems associated with currently available drugs are the tendency to develop resistance and the lack of clearance of the virus from the hepatocytes. There is clearly a need to identify new drugs that can benefit patients with chronic hepatitis B infections. REP 9AC is a 40mer phosphorothioate oligonucleotide that has been shown to have low toxicity and to be highly effective to treat hepatitis B infection in animals. It has been shown to be effective in protecting animal from infection and to treat animals already infected.

The efficacy of REP 9AC (REP 2055) in duck hepatitis B has been tested in collaboration with Dr. Allison Jilbert (University of Adelaide, Australia), who is a recognized expert on HBV infections. These results suggest that REP 2055 can completely eliminate the disease in a large proportion (50%) of animals following only 4 weeks of treatment. In other words, following cessation of the treatment, the viral titer does not return. If these results are replicated in humans, this will result in a paradigm shift in how patients with hepatitis B are treated. Currently available drugs can only control the disease. Once they are stopped, the viral titer returns.

This proposed study is designed to demonstrate that REP9AC can be well tolerated when given to human patients chronically infected with HBV and to evaluate if a reduction of viral titers can be observed when REP 9AC is administered as a monotherapy. Current interim data analysis from the REP 101 trial indicates the following:

1. REP 9AC is generally well tolerated at doses up to 600mg / week in all patients currently enrolled and in HBV patients at 400mg / day (for seven continuous days).
2. REP 9AC has resulted in both HBV patients achieving protective seroconversion (anti-HBs) and clearance of HBV DNA and HBsAg in their blood by 23 weeks after initiation of treatment.
3. Increasing frequency and dose of REP 9AC treatment at the start of therapy may provide more rapid seroconversion of HBV patients.
4. Increasing frequency and dose of REP 9AC treatment at the start of therapy may provide better efficacy for HCV patients.