Heplisav: Phase III data

Top-line data from a double-blind, U.S. Phase III trial in 2,449 healthy volunteers ages 40-70 showed that Heplisav met the primary and secondary immunogenicity endpoints of non-inferiority and superiority, respectively, to Engerix-B in the proportion of subjects achieving a seroprotective immune response, defined as anti-HBsAg antibody levels of >=10 mlU/mL, measured at 8 weeks after the last dose of the vaccine vs. Engerix-B (90% vs. 70%). In a lot-to-lot consistency analysis of 3 consecutively manufactured lots of Heplisav, the vaccine missed the pre-specified consistency criteria as measured by both geometric mean antibody concentration and seroprotection rates at 8 weeks after the last dose, but met the criteria for both consistency measurements at weeks 12, 18, 24 and 28. Dynavax said the pre-specified criteria for consistency were a lower and upper bound of the 95% CI of 66% and 150%, respectively. Detailed results were not disclosed. Dynavax said the data supporting the consistency of the 3 consecutively manufactured lots of Heplisav have been submitted to FDA, and that the company expects confirmation that the lots were consistent from the agency in the near future.

Heplisav was well tolerated with no cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis or Wegener's granulomatosis reported. Additionally, there were 3 new onset autoimmune adverse events, none of which the company said were serious adverse events, in patients receiving Heplisav. Subjects received 2 doses of Heplisav at months 0 and 1 or 3 doses of Engerix-B at months 0, 1 and 6. Data will be presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago in September. ...