GI-5005 for chronic hepatitis C infection

Chronic hepatitis C (HCV) infection, a viral liver disease, is a major health epidemic worldwide.  Currently, there are approximately 170 million people worldwide who are infected with the hepatitis C virus.  Of these, 4 million live in the United States with an additional 5 million in Western Europe.  Approximately 20-30% of all hepatitis C patients will face life threatening complications as a result of their disease. Hepatitis C accounts for 20% of cases of acute hepatitis, 70% of cases of chronic hepatitis, 40% of cases of end-stage cirrhosis, 60% of cases of hepatocellular carcinoma and 30% of liver transplants in the United States.  The incidence of new symptomatic infections of hepatitis C has been estimated to be 13 cases/100,000 persons annually.  For every one person who is infected with the AIDS virus, there are more than four infected with hepatitis C. Currently, 8,000 to 10,000 deaths each year are attributed to hepatitis C.

The GI-5005 Tarmogen

The GI-5005 Tarmogen expresses a fusion protein encompassing sequences from both HCV NS3 and Core proteins.  NS3 and Core are abundantly expressed in infected cells, are required for viral replication and contain targets that are recognized by both CD4+ "helper" and CD8+ "killer" T cells.  Both the Core and NS3 proteins are highly conserved among HCV genotypes 1a and 1b, the HCV strains most prevalent in the U.S.   In December 2007, GI-5005 initiated a multi-center, randomized, Phase 2 study in combination with standard of care (pegylated interferon plus ribavirin).

Phase 1b Clinical Data

Study GI-5005-01 was a double-blind, placebo-controlled, multi-center, dose-escalation therapeutic trial evaluating the subcutaneous administration of 7 doses of GI-5005 as a monotherapy. 71 patients with chronic HCV at nine centers were enrolled in this study (53 treated, 18 placebo).  

In the Phase 1b trial, GI-5005 demonstrated:

• An excellent safety profile, with no product-related dose limiting toxicities (DLTs) or serious adverse events (SAEs) to date.
• Biologic / immune activity by converting subjects from an immune response profile associated with chronic infection to one similar to subjects who clear the virus naturally during the acute phase, as measured by ELISPOT assay.
• Strong trends for a dose dependent response in the percent of subjects that normalized their ALT (alanine aminotransferase - a marker of liver damage) compared with placebo.

             -    0%    placebo subjects normalized their ALT levels on study 
             -  11%    from the first 4 dose groups combined (through 10YU) normalized ALT
             -  43%    of the 20YU cohort normalized ALT levels on treatment
             -  50%    of the 40YU cohort normalized ALT levels on treatment

• Viral load reductions in GI-5005 treated patients up to -1.4 log10.
• No placebo subjects (0 / 19) normalized their ALT on study drug, or had near log10 reductions of viral load on study drug.

A randomized Phase 2 study evaluating GI-5005 plus standard of care (pegIFN + ribavirin) versus standard of care alone was initiated December 2007 and completed enrollment of 140 subjects in May 2008.  This study enrolled patients with chronic genotype 1 hepatitis C infection who were either treatment naïve or non-responders to a prior interferon based regimen using pegylated or non-pegylated interferon alpha with ribavirin. GI-5005 salvage of in-study Standard of Care failures will also be explored in this trial. Click here for study details.