GS-4774 for chronic hepatitis B infection (HBV)
GS-4774 is a therapeutic vaccine engineered to activate an HBV-specific T cell immune response to reduce the number of cells containing HBV.
Chronic HBV infection affects approximately 400 million people worldwide. While antiviral drugs have been used effectively to control this disease, cure rates are very low, with less than eight percent cured after four years of daily oral antiviral therapy.
Vaccination has dramatically reduced the prevalence rates among children in Western nations. However, mother-to-newborn transmission, especially in Asia, remains a common source of new infection. Current treatment for chronic HBV includes oral antiviral therapy to suppress virus replication. These antiviral products have been effectively used to suppress the virus from replicating, effectively controlling the disease. However, most patients do not achieve permanent clearance of the virus on treatment and require long term therapy.
GS-4774 is being developed as a therapeutic vaccine designed to generate T cell immune responses against cells containing HBV antigens in combination with antiviral therapy with the goal of increasing the cure rate in patients with chronic HBV infection. The GS-4774 Tarmogen expresses a fusion protein utilizing sequences of the hepatitis B virus contained in the four major HBV genotypes worldwide, in order to ensure applicability for this product across multiple markets.
In August 2013, we completed a Phase 1 clinical trial of GS-4774 in 60 healthy volunteers. Twenty subjects were enrolled to one of three dose groups. The Phase 1 results indicated that GS-4774 elicited HBV specific T cell immune responses in all three dose groups. Overall, eighty-eight percent of subjects across all three dose groups responded to receiving GS-4774 by at least one measure of T cell immune response.
Phase 2 – virally suppressed subjects
Gilead initiated a Phase 2 clinical trial in September 2013 investigating GS-4774 in combination with ongoing oral antiviral treatment in patients with chronic HBV infection. This Phase 2 clinical trial is designed to enroll 175 patients in a randomized, open-label design comparing different doses of GS-4774, administered in combination with oral antiviral therapy vs. antiviral treatment alone. The primary endpoint for this trial is decline in serum HBV surface antigen, or HBsAg. This trial is fully-enrolled, and 48-week results are expected to be available in the first half of 2015. These results may be submitted to an upcoming scientific conference.
Phase 2 – treatment naïve subjects
Gilead initiated a second Phase 2 clinical trial in July 2014 investigating GS-4774 in patients with chronic HBV infection who are currently not receiving treatment. This Phase 2 clinical trial is designed to enroll 175 patients in a randomized, open-label design comparing different doses of GS-4774, administered in combination with tenofovir disoproxil fumarate, or TDF, vs. TDF alone. The primary endpoint for this trial is decline in serum HBV surface antigen.