New Hepatitis B Vaccine Begins Phase 3 Trial

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New Hepatitis B Vaccine Begins Phase 3 Trial
By Dynavax Technologies, Jun 24, 2005 - 12:06:38 PM

Dynavax Technologies Corporation announced the initiation of a pivotal Phase 3 clinical trial of its hepatitis B (HBV) vaccine. The pivotal Phase 3 trial is designed to compare the effectiveness of Dynavax's HBV vaccine to GlaxoSmithKline's Engerix-B(R) HBV vaccine in an older adult population that is more difficult to immunize with conventional vaccine.

A second pivotal Phase 3 trial in a younger adult population to be conducted in Europe and Canada is anticipated to begin in early 2006. Assuming positive data from these trials, Dynavax could potentially file a BLA for its HBV vaccine in 2007.

Dynavax's HBV vaccine is based on its proprietary immunostimulatory sequence (ISS) that specifically targets Toll-Like Receptor 9 (TLR-9) 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.

"The initiation of Phase 3 testing of our ISS-based HBV vaccine is a major milestone for Dynavax," said Dino Dina, MD, president and chief executive officer. "We believe our vaccine is the first TLR-9 agonist-based product to reach late-stage development, and represents an important corporate as well as technological achievement."

Continued Dr. Dina: "Our HBV vaccine has consistently demonstrated superior effectiveness over the industry standard vaccine in earlier clinical trials. Our registration and commercialization strategy focuses on target populations where the clinical need for an enhanced vaccine is greatest and where we believe we can achieve a significant commercial return. These populations include hemodialysis patients, healthcare and emergency response personnel, people infected with HIV or hepatitis C, and people who receive multiple transfusions. These populations represent high value, underserved markets, as their needs for enhanced efficacy, faster response and shorter vaccination regimens are clear."

The Phase 3 trial will enroll more than 400 seronegative adults (with no detectable HBV antibodies), aged 40-70, and will take place at study sites in Singapore, Taiwan, Korea and the Philippines. The trial will be one-to-one randomized and double-blinded. One group will receive three doses of Dynavax's HBV vaccine, administered at a dose of 20 micrograms HBsAg plus 3 milligrams of ISS, by intramuscular injection at zero, two months and six months. The other group will receive three doses of Engerix-B administered at a dose of 20 micrograms HBsAg by intramuscular injection at zero, one and six months. The primary endpoint is seroprotection four weeks after the third vaccination (at month seven). Study subjects will also be followed for an additional five months. The trial is anticipated to be completed in the second half of 2006.

Dynavax also plans to conduct additional trials in selected high-risk populations, such as dialysis patients, in targeted markets in Europe, Canada and potentially in the United States.

Dynavax has previously reported that the primary endpoint analysis of a randomized, double-blind Phase 2/3 trial in older adults showed statistically significant superiority in protective antibody response and robustness of protective effect after three vaccinations compared to Engerix-B. Results from a double-blind Phase 2 clinical trial conducted in young adults (18-28 years) also showed protective antibody responses were achieved faster (two vaccinations over two months compared to three over six months) and were maintained longer with Dynavax's HBV vaccine than with Engerix-B.

Dynavax is currently evaluating global commercialization and distribution strategies for its HBV vaccine. Dynavax has a long-term supply contract with Switzerland-based Berna Biotech that includes a commercialization option. The companies are at the early stages of discussing this option.

The Public Health Challenge of Hepatitis B

Hepatitis B is a highly contagious, chronic infectious disease. It is estimated that one out of three people in the world is infected with HBV, and that 10-30 million people in the world become infected with HBV every year. Chronic HBV infections cause 80% of all primary liver cancers, and are the leading cause of liver transplantation.

Vaccination is central to managing the spread of the disease, particularly in regions of the world with large numbers of chronically infected individuals. While many countries have instituted infant vaccination programs, compliance is not optimal. There are large numbers of individuals born prior to the implementation of these programs who are unvaccinated and are at risk for the disease. Not all individuals respond to currently approved vaccines.

Compliance with the immunization regimen of currently approved HBV vaccines is a significant challenge, as many patients fail to receive all three doses. According to a survey of U.S. adolescents and adults published by the Centers for Disease Control and Prevention, only 53% of those who received the first dose of vaccine received the second dose of vaccine and only 30% received the third. Dynavax believes that compliance rates in other countries are similar, if not lower.

HBV vaccination represents today approximately $1 billion in sales worldwide. In many parts of the world such as China, Southeast Asia and India, and Eastern Europe, vaccination is managed through public health organizations and the price of vaccines used on a mass scale is very low. In other areas such as the US, Western Europe and high-value markets in Asia and the rest of the world, the private vaccine market is robust and differentiated products have the potential to command premium pricing. Dynavax's HBV commercial strategy targets these high value markets worldwide.

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