Dynavax Technologies Corporation has announced statistically significant results from the primary endpoint analysis of a phase 3 trial comparing Heplisav, its hepatitis B virus (HBV) vaccine, to GlaxoSmithKline's Engerix-B vaccine in a difficult to immunize population of older adults. The primary endpoint is seroprotection four weeks after the third immunization.

The data show that after three doses, Heplisav provided seroprotection to 100 per cent of subjects versus 73.1 per cent for Engerix-B. The greatest difference in seroprotection after three doses was seen in subjects 56 to 70 years of age where Heplisav provided 100 per cent seroprotection and Engerix-B provided 56.1 per cent. Data for the entire study population show that after two doses, Heplisav provided 98.5 per cent seroprotection versus Engerix-B's 25 per cent. Furthermore, Heplisav provided a level of immunity as measured by geometric mean concentrations of anti-HBsAg antibodies 18.5 times higher than Engerix-B four weeks after the third dose.

According to Dino Dina, M.D., president and chief executive officer, "These results once again demonstrate Heplisav's superior effectiveness over conventional hepatitis B vaccine. The most striking outcome from the trial is the vaccine's ability to generate 98.5 per cent protection after two doses in older difficult to immunize adults. This has the potential to drive an important change in the way people are immunized against hepatitis B."

The phase 3 trial enrolled more than 400 seronegative subjects, 40 to 70 years of age, at study sites in Singapore, Korea and the Philippines. One group of subjects received three doses of Dynavax's HBV vaccine; the other group received three doses of Engerix-B.

In December 2005, Dynavax reported the results of a smaller phase 2/3 trial in older adults as part of a poster at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), specifically the superiority of Heplisav compared to Engerix-B relative to the primary efficacy endpoint of seroprotection (100 per cent in the Heplisav-treated group compared to 90.5 per cent in the Engerix-B treated group; p = 0.033) and relative to geometric mean concentration or GMC (1698 compared to 569 mIU/mL; p = 0.023). Dr. Lim Seng Gee, study investigator, also showed that subjects treated with Heplisav experienced more durable seroprotection. At week 50, the Heplisav-treated group measured 100 per cent seroprotection and GMC of 499 mIU/mL compared to 86 per cent and 153 mIU/mL for the Engerix-B treated group (p = 0.009 and p = 0.005, respectively). The trial was conducted in 89 older adults, 40 to 70 years of age. Heplisav was well tolerated and did not induce serious adverse effects.

Dynavax plans to pursue approval of a two-dose regimen administered at zero and one month, and expects to initiate multi-center, international phase 3 trials in Europe, Canada and the US before the year-end, comparing the two-dose regimen against Engerix-B in patients from 11 to 55 years of age. The first dosing is expected in Canada, followed in early 2007 by dosing in the US and in Europe. These trials are expected to be completed in 2008.

Dynavax's HBV vaccine is based on its proprietary immunostimulatory sequence (ISS) that specifically targets Toll-Like Receptor 9 (TLR9) to stimulate an innate immune response. Dynavax's HBV vaccine combines ISS with HBV surface antigen (HBsAg) and is designed to significantly enhance the level, speed and longevity of protection. Dynavax indicates that as a result of its acquisition of Rhein Biotech in April 2006, the company has secured manufacturing capabilities in Dusseldorf, Germany for producing both clinical and commercial quantities of the vaccine.