GI-5005 contains a fusion of two hepatitis C proteins, NS3 and Core, which are highly conserved across HCV genotypes and are recognized by T cells. GI-5005 is engineered to activate an HCV-specific T cell immune response, resulting in the reduction of cells containing viral antigens.
The World Health Organization estimates that up to 170 million people globally are infected with HCV, with three to four million new infections each year. Approximately 20% to 30% of all HCV patients will face life-threatening complications as a result of their disease. In industrialized countries, HCV accounts for 40% of cases of end-stage cirrhosis, 60% of cases of hepatocellular carcinoma and 30% of liver transplants.
GI-5005 is designed to complement therapeutic approaches that suppress replication of HCV, including interferon- and small molecule-based regimens, without adding meaningful toxicities to the regimen. We believe GI-5005 is the first therapeutic vaccine to demonstrate a clinically meaningful outcome in patients with a chronic infectious disease, and we are evaluating the potential role of GI-5005 in difficult-to-treat chronic HCV patients.
GI-5005-02 was a randomized Phase 2b clinical trial evaluating 40YU GI-5005 plus pegIFN/ribavirin compared to pegIFN/ribavirin alone in subjects with chronic genotype 1 HCV infection. The study was stratified by prior response to interferon plus ribavirin therapy. Seventy-three percent of subjects randomized had not previously been treated with interferon-based therapy, and 27% of subjects had not previously responded to interferon-based regimens.
Study results included:
- Overall, GI-5005 when used in combination with pegIFN/ribavirin demonstrated an improvement in each of the following:
- 43 of 68 subjects, or 63%, receiving GI-5005 plus pegIFN/ribavirin compared to 29 of 65 subjects, or 45%, receiving pegIFN/ribavirin alone had clearance of virus at the end of treatment;
- 29 of 50 subjects not previously treated with interferon-based therapy, or 58%, receiving GI-5005 plus pegIFN/ribavirin compared to 22 of 46 such subjects, or 48%, receiving pegIFN/ribavirin alone achieved sustained virologic response at 24 weeks following completion of therapy (SVR24); and
- 3 of 18 subjects who had previously not responded to interferon-based regimens, or 17%, receiving GI-5005 plus pegIFN/ribavirin compared to 1 of 19 such subjects, or 5%, receiving pegIFN/ribavirin alone achieved SVR24;
- Responses differed by IL28B genotype in subjects who had not received prior treatment. For example, the largest improvement in SVR24 was observed in subjects with the most difficult-to-treat IL28B genotype, T/T, with three of five subjects, or 60%, receiving GI-5005 plus pegIFN/ribavirin achieving SVR24 compared to none of the five subjects receiving pegIFN/ribavirin alone. Additionally, the largest immune effect in subjects receiving GI-5005 plus pegIFN/ribavirin, measured by the number of HCV-specific T cells, was seen in subjects with the T/T genotype;
- 37 of 61 subjects, or 61%, receiving GI-5005 plus pegIFN/ribavirin compared to 16 of 44 subjects, or 36%, receiving pegIFN/ribavirin alone showed normalized ALT levels at the completion of therapy;
- GI-5005 was generally well tolerated;
- The trial was not powered to achieve statistical significance and the difference observed in SVR24 did not achieve statistical significance.
We have expanded the GI-5005-02 clinical trial to enroll 19 additional difficult-to-treat IL28B T/T subjects. These subjects have been randomized to either GI-5005 plus pegIFN/ribavirin or pegIFN/ribavirin alone to further evaluate the magnitude of the potential treatment effect of GI-5005.