SAN DIEGO, CA—Two doses of the investigational hepatitis B vaccine, HEPLISAV, administered over 4 weeks induced significantly higher rates of and earlier seroprotection than Engerix-B given as 3 doses over 24 weeks, results of two pivotal Phase 3 trials concluded at IDWeek 2012.
Two multicenter trials of the two vaccines were conducted to determine immunogenicity in subjects in the age range for the proposed indication for HEPLISAV, noted Robert Janssen, MD, from Dynavax Technologies, Berkeley, CA. Dynavax has submitted a Biologics License Application to the U.S. Food and Drug Administration for an indication of prevention of hepatitis B infection in individuals 18 to 70 years old.
This study compared the seroprotection rates in analyses that combined the modified intent-to-treat populations of the two trials, which randomly assigned subjects to HEPLISAV (20mcg rHBsAg combined with 3,000mcg 1018 ISS adjuvant, a toll-like receptor 9 agonist) given at 0 and 4 weeks (placebo at 24 weeks) or Engerix-B (20mcg rHBsAg with 500mcg aluminum hydroxide) given at 0, 4, and 24 weeks.
In the first trial, subjects 18 to 55 years old were randomized 3:1 to receive HEPLISAV (n=1,820) or Engerix-B (n=608). In the second trial, subjects 40 to 70 years old were randomized 4:1 to receive HEPLISAV (n=1,969) or Engerix-B (n=483). In both trials, the difference in seroprotection rates (defined as the percentage with anti-HBs ≥10mIU/mL) between HEPLISAV and Engerix-B met the superiority objective.
They found peak seroprotection rates of HEPLISAV to be significantly higher than those of Engerix-B in subjects 18 to 70 years of age (96.4% vs. 76.7%, respectively) as well as in the population stratified by age: 99.6% vs. 88.6% in those 18 to 39 years old and 95.5% vs. 72.7% in the 40-to-70-year-old group (all P<0.0001).
Beginning at Week 4, HEPLISAV also induced significantly higher seroprotection rates than Engerix-B at each study visit. Safety profiles of the two vaccines were generally similar, study investigators reported.