Source: DGNews  |  Posted 4 years ago

By John Gever

CHICAGO, IL -- September 20, 2007 -- An investigational hepatitis B virus (HBV) vaccine combining HBV surface antigens (HBsAg) with a synthetic oligonucleotide outperformed a standard commercial vaccine in a phase 3 study, according to research presented here at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

The oligonucleotide is a 22-mer phosphorothioate sequence called 1018 immunostimulatory sequence (1018 ISS), intended to boost immune responses to pathogen-specific antigens.

The vaccine that combines 1018 ISS and HBsAg is called Heplisav(TM). Its performance in the phase 3 study compared with Engerix-B (Hepatitis B vaccine [recombinant]) was described at a poster session on September 19th by Eduardo B. Martins, MD, PhD, Vice President of Clinical Development, Dynavax Technologies Corporation, Berkeley, California.

The randomized, double-blind study was conducted in South Korea, Singapore, and the Philippines on 412 subjects aged 40 to 70 years.

Subjects received three doses of either Heplisav or Engerix-B and were tested periodically for 50 weeks after the first dose for blood levels of anti-HBsAg antibodies. The primary seroprotection measure was the percentage of subjects with antibody levels above 10 mIU/mL.

Anti-HBsAg antibody levels were measured 4 weeks after administration of each dose of 20 mcg of Engerix-B at 0, 1, and 6 months or 20 mcg of HBsAg plus 3,000 mcg of 1018 ISS at 0, 2, and 6 months, and at 50 weeks after the initial dose.

Heplisav produced faster and more complete seroprotection than did Engerix-B, according to the poster. By 12 weeks after the first vaccine dose, 97% of Heplisav subjects had reached the target antibody level compared with 23% of the Engerix-B group. At week 28, the entire Heplisav group had achieved the target level versus 73% of Engerix-B subjects.

The 100% seroprotection with Heplisav continued to week 50, while in the Engerix-B group the proportion of protected individuals did not increase further, and in fact decreased slightly to 69% at week 50.

The high degree of seroprotection in this study is consistent with earlier clinical results, according to Dr. Martins. "It's been 100% in every trial so far," he said.

Adverse events were generally mild and did not differ significantly between vaccines. About 40% of subjects in each group experienced some kind of reaction event, such as injection-site inflammation, malaise, headache, or fatigue. No severe adverse effects were seen.

"Vaccination with HBsAg+1018 ISS could substantially improve protection against HBV in adults," the researchers concluded.

Dr. Martins said additional phase 3 studies are now in progress in different locations, with an eventual goal of enrolling some 4,000 subjects overall. If the results are favorable, Dynavax plans to seek US marketing approval in late 2008.

[Presentation title: A Phase 3 Study Comparing Vaccination With Hepatitis B Surface Antigen (HBsAg) Combined With Immunostimulatory Phosphorotioate Oligonucleotide to Conventional Hepatitis B Vaccine in Older Adults. Abstract G-1701]