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HBV Vaccine Flops in Mid-Stage Trial

Vaccine no more effective than oral antiviral therapy

Disappointing results have been reported from a stage II study of GS-4774 (GlobeImmune, Inc./Gilead Sciences) in patients with chronic hepatitis B virus (HBV) infection receiving long-term viral suppression with oral antiviral therapy (OAT).

The new study enrolled 178 patients in a randomized, open-label design to compare three doses of GS-4774 (2 yeast units [YUs], 10 YUs, or 40 YUs) administered in combination with OAT compared with OAT alone. One YU is equal to 10 million yeast cells.

Patients treated with the highest dose of GS-4774 plus ongoing OAT did not show a reduction in hepatitis B surface antigen (HBsAg) at week 24 –– the study’s primary endpoint –– but at 48 weeks had a mean –0.17 log10 reduction of HBsAg compared with a –0.04 log10 reduction in the OAT group (difference not significant).

Three patients receiving the highest dose of GS-4774 had HBsAg reductions of between –0.94 and –3.89 log10 at 48 weeks. There was no difference in HBsAg reductions between the two lowest-dose groups and the control arm at 48 weeks. Further characterization of the T- cell response to GS-4774 and its association with HBsAg changes is ongoing.

GS-4774 was found to be generally safe and well tolerated, with injection-site reactions identified as the primary adverse event.

GS-4774 is a therapeutic vaccine engineered to activate an HBV-specific T-cell immune response to clear viruses from cells containing HBV. GS-4774 expresses a fusion protein using sequences of the HBV contained in the four major HBV genotypes worldwide. The vaccine is being developed to increase the HBsAg seroconversion rate when used in combination with OAT.

Chronic HBV infection is the most common serious liver infection in the world, affecting approximately 400 million people. While approximately 80% of acutely infected patients clear the virus without treatment (predominantly through a T-cell immune response), there is currently no cure for most chronically infected patients. Untreated chronic HBV infection is associated with a significant increase in related diseases, including liver cirrhosis, hepatic decompensation, and liver cancer. Mortality is also increased in patients with chronic HBV infection, with 25% to 40% of patients dying from complications of liver disease.

Source: GlobeImmune, Inc.; May 27, 2015.


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