Dynavax Announces Positive Interim Results from Phase II/III Hepatitis B Vaccine Trial

BERKELEY, Calif. -- Dynavax Technologies announced that data from an interim analysis of the company's hepatitis B virus (HBV) vaccine phase II/III clinical trial showed statistically significant superiority in protective antibody response and robustness of protective effect after two vaccinations when compared to GlaxoSmithKline's Engerix-B(TM) vaccine in an older adult population that is traditionally more difficult to immunize with conventional vaccine. The primary endpoint of the ongoing phase II/III trial is seroprotection four weeks after administration of the third dose. Based on these positive interim results, as well as previously reported data showing that Dynavax's HBV vaccine induced more rapid immunogenicity and more durable protective response compared to Engerix-B in healthy young adults, Dynavax intends to pursue a broad phase III clinical program in multiple age groups, anticipated to begin in mid-2005. Dynavax's HBV vaccine combines its proprietary immunostimulatory sequence (ISS) co-administered with HBV surface antigen (HBsAg), designed to significantly enhance the level, speed and longevity of protection. The study is being conducted by Dr. Lim Seng Gee at the National University Hospital, and Dr. Chow Wan Cheng, at the Singapore General Hospital. The phase II/III trial should be completed in mid-2005.

"These positive interim phase II/III results strengthen our confidence that our HBV vaccine can provide important advantages in terms of rapidity and level of seroprotection in an adult population known to be difficult to immunize, and increase our belief that our vaccine represents a significant commercial opportunity for our company," said Dino Dina, MD, president and chief executive officer. "Despite the prevalence of HBV vaccination in major markets worldwide, there are serious limitations to the effectiveness of conventional vaccines due to the widespread challenge of patient compliance with the required three dose regimen. We intend to implement a broad, confirmatory phase III program in mid 2005 in multiple populations, as we believe that Dynavax's HBV vaccine has the potential to change vaccination practices, establish new industry standards of effectiveness, and provide significant public health and pharmacoeconomic benefits."

Phase II/III Trial Design and Results

The ongoing phase II/III clinical trial is a double-blind, controlled study. On an intent-to-treat basis, the study involved 88 healthy, seronegative subjects (with no detectable HBV antibodies) aged 40-70, four of whom had a history of smoking and 26 of whom were overweight (body mass index greater than 27 kilograms per meter-squared). The subjects were randomized into two treatment groups. One group received three doses of Dynavax's HBV vaccine, administered at a dose of 20 micrograms HBsAg plus three milligrams of ISS, by intramuscular injection at zero, two and six months. The other group received three doses of Engerix-B administered at a dose of 20 micrograms HBsAg by intramuscular injection at zero, one and six months. The interim analysis was based on results four weeks after administration of the second dose. Dynavax plans to follow up with subjects for an additional five months and anticipates completing the study in mid 2005.

A protective antibody response is defined in titers greater than or equal to 10 mIU/mL (milli-international units per milliliter). The results of the interim phase II/III trial are expressed in geometric mean titers (GMT).

In November 2004, Dynavax presented data from a randomized, double-blind phase II clinical trial of the company's prophylactic hepatitis B virus (HBV) vaccine conducted in young adults (18-28 years) that showed superior results compared to GlaxoSmithKline's Engerix-B(R) vaccine. Protective antibody responses were achieved faster and were maintained longer with Dynavax's HBV vaccine than with Engerix-B.

Planned Phase III Clinical Trial Design

Dynavax intends to initiate phase III clinical trials of its HBV vaccine targeting adolescent, young adult and older adult populations. The first of these trials involving older adults in Asia is anticipated to begin in mid-2005. Phase III studies in young adults are anticipated to begin later in 2005 in Canada and Europe. These trials will be designed as confirmatory and could be completed in 2006. The trials will be designed to compare Dynavax's HBV vaccine with Engerix-B and could include different dosing regimens for different populations. One potential target population is kidney dialysis patients, all of whom must be vaccinated against HBV, and for whom a shorter and more effective immunization regimen could have significant therapeutic benefit.

Dynavax is currently evaluating commercialization and distribution strategies for its HBV vaccine in countries outside of the United States. In 2003, Dynavax and Berna Biotech (Bern, Switzerland) entered into a clinical and commercial supply agreement for HBV surface antigen. Dynavax estimates the HBV vaccine market outside of the United States to be approximately $500 million.

Source: Dynavax Technologies Corporation

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