I suppose the muted response is due to the highlighted remarks.
Dynavax's Hepatitis B Vaccine Shows More Rapid Immunogenicity, More Durable Protective Response Than Engerix-B in Phase 2 Clinical Trial
Monday November 1, 6:00 am ET
100% Protective Response Sustained More Than One Year Later After Two-Dose Regimen of Dynavax's ISS-based Vaccine
BERKELEY, Calif., Nov. 1 /PRNewswire-FirstCall/ -- Dynavax Technologies (Nasdaq: DVAX - News) announced that data from a randomized, double-blind Phase 2 clinical trial of the company's prophylactic hepatitis B virus (HBV) vaccine showed superior results compared to GlaxoSmithKline's Engerix-B® vaccine. Protective antibody responses were achieved faster and were maintained longer with Dynavax's HBV vaccine than with Engerix-B. 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.
Results from the completed Phase 2 clinical trial demonstrated that recipients of Dynavax's HBV-ISS vaccine more rapidly achieved seroprotection after each dose when compared to Engerix-B (79% and 100% seroprotection one month after one and two doses administered over two months, respectively, compared to 12% and 64% for the Engerix-B-treated group). The seroprotection achieved by the HBV-ISS treated group after only two doses was sustained more than one year later. The Engerix-B treated group required three doses to achieve 98% seroprotection that fell to 90% six months later. The company believes that results from this Phase 2 clinical trial conducted in healthy young adults, combined with anticipated interim results from its Phase 2/3 clinical trial currently underway in Singapore in an older, more difficult-to-treat adult population, should provide a strong rationale for initiating a confirmatory Phase 3 program in mid-2005.
"From a clinical as well as a public health perspective, the benefit of achieving and maintaining a 100% protective antibody response after only two doses in two months of Dynavax's ISS-based HBV vaccine is medically meaningful, as many individuals do not comply with a two or three-dose immunization regimen that must be carried out over six months," said Scott A. Halperin, M.D., of Dalhousie University, Halifax, Nova Scotia, Canada, the principal investigator in the Phase 2 clinical trial. "Hepatitis B infection represents a serious and growing societal challenge especially in countries outside of North America and Western Europe where the incidence of the disease is increasing, and the need for more effective preventive intervention is acute."
"We believe that Dynavax's ISS-based HBV vaccine has demonstrated significant advantages over the Engerix-B vaccine, and that our approach represents an important potential alternative to currently marketed vaccines that require multiple doses and demand a high level of patient compliance while producing a suboptimal level of seroprotection," said Dino Dina, M.D., president and chief executive officer, Dynavax. "Our strategy is to aggressively pursue completion of our Phase 3 hepatitis B prophylaxis program and, assuming a positive outcome, cultivate entry points into markets outside the US that have very large at-risk populations that are currently underserved by available vaccines."
The Phase 2 data were presented in a late-breaker poster session at the 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The data were presented by Dr. Halperin and by Daniel Levitt, M.D., Ph.D., vice president and chief medical officer of Dynavax, in a poster entitled, "Hepatitis B Virus Surface Antigen (HBV) Co-administered with an Immunostimulatory Phosphorothioate Oligonucleotide (HBV-ISS) Achieves Protective Antibody Levels More Quickly and with Fewer Doses than a Licensed Hepatitis B Vaccine." The poster can be viewed online at www.icaac.org.
Study Design
The Phase 2 clinical trial enrolled 99 healthy, seronegative 18-28 year-old adults (65% female; mean age 22.6 years). Participants were randomized to two treatment groups. One group received two doses of HBV-ISS, administered at a dose of 20 micrograms HBsAg plus 3 milligrams of ISS, by intramuscular injection at zero (0) and at eight (8) weeks, and received a placebo at 24 weeks. The other group received three doses of Engerix-B administered at a dose of 20 micrograms HBsAg by intramuscular injection, on the same zero/eight/24-week schedule. Adverse events were collected one and four weeks after each dose. Antibody levels were measured four weeks after the first dose; before and at one and four weeks after the second dose; before and at one and four weeks after the third dose; and at one year.
Study Results
A protective antibody response is defined in titers as greater than or equal to 10 mIU/mL (milli-international units per milliliter). The results of the Phase 2 trial, all expressed in geometric mean titers, showed that:
-- Four weeks following the first dose, 79% of the HBV-ISS treated group
had a protective antibody response (23.0 mIU/mL) compared to 12%
(1.87 mIU/ML) of the Engerix-B recipient group.
-- At one week following the second dose, 100% of the HBV-ISS treated
group had protective levels compared to 18% of the Engerix-B treated
group (1603 versus 2.40 mIU/mL, respectively).
-- By four weeks following the second dose, the HBV-ISS group still had
protective levels of 100% compared to 64% for the Engerix-B treated
group (2074 versus 32.3 mIU/mL, respectively).
-- At four weeks following administration of the third dose to the
Engerix-B treated group, 98% had protective levels (5239 mIU/mL) that
fell to 89% six months later (617 mIU/mL).
-- Despite receiving a placebo at the third dosing schedule, the HBV-ISS
treated group's protective levels remained at 100% four weeks later and
more than one year later (1408 and 851 mIU/mL, respectively).
Rates of fever, muscle aches, nausea, vomiting diarrhea, headache, fatigue, chills and joint pain were low and similar in both treated groups. Headache and fatigue were the most common systemic adverse events in up to one third of both groups. Mild injection site reactions were more common after administration of HBV-ISS. Tenderness was reported by 74-83% of the HBV-ISS treated group versus 34-58% of the Engerix-B treated group (p equal to or less than 0.029).
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