Washington Editor

Shares in Dynavax Technologies Corp. soared 32 percent Wednesday on positive Phase III data for its hepatitis B vaccine, Heplisav.

The stock (NASDAQ:DVAX) climbed $2.39 to close at $9.79 after the Berkeley, Calif.-based company released results from a trial comparing the investigational vaccine to Engerix-B (from GlaxoSmithKline plc) in a difficult-to-immunize population of older Asian adults between 40 and 70 years old. Though the 400-patient study is seen as "supportive but not critical" to eventual marketing applications, said company President and CEO Dino Dina, the results point to a "potential to drive an important change in the way adults are immunized against hepatitis B."

In particular, there was a statistically significant difference in the primary endpoint, seroprotection four weeks after the third immunization, a standard measure for approval of already-marketed hepatitis B vaccines. The analysis showed that 100 percent of Heplisav-treated subjects achieved seroprotection, compared to 73.1 percent of those vaccinated with Engerix-B (p<0.0001).

In addition, several other measures pointed to the superiority of Heplisav, a product that is based on the company's immunostimulatory sequence that specifically targets Toll-like receptor 9 to stimulate an innate immune response.

For example, the investigational vaccine began working much more quickly, with Heplisav providing 98.5 percent seroprotection after two doses compared to 25 percent for Engerix-B. 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. The "most striking" benefit was demonstrated in subjects between 56 and 70, again with all Heplisav-treated subjects achieving seroprotection, compared to 56.1 percent for Engerix-B, Dina said.

"These achievements give us confidence that our studies in difficult-to-immunize groups, as well as other adults, will be successful," he added. "We believe that we have a vaccine that is clearly differentiated from competitive products."

All the findings correlate nicely with a previous Phase II/III study in 89 adults between 40 and 70. Those data, reported at last year's Interscience Conference on Antimicrobial Agents and Chemotherapy, showed that 100 percent in the Heplisav-treated group achieved seroprotection compared to 90.5 percent in the Engerix-B treated group (p=0.033), and Heplisav produced a geometric mean concentration of 1,698 mIU/mL compared to 569 mIU/mL for Engerix-B (p=0.023). In addition, both those measures were more durable almost a year out in the Heplisav-treated group.

Down the road, Dynavax plans to seek approval of a two-dose regimen administered a month apart, establishing Heplisav as "equivalent or better" at providing protection levels than conventional vaccines that require three doses over six months, Dina said. To support that plan, the company expects to begin international Phase III trials in Europe, Canada and the U.S. before the end of the year to compare such a regimen of Heplisav against Engerix-B in patients between 11 and 55, a younger population that he said has responded "proportionally better."

Those studies are expected to be completed in 2008.

"With continued success in our programs," Dina said, "we'll be able to address unmet medical and commercial needs in the prevention of hepatitis B infection, specifically providing faster and more durable seroprotection."

Looking ahead, the company is considering multiple target populations, including international adult travelers, health care workers and adolescents, as well as end-stage renal disease or dialysis patients who don't respond well to existing vaccines. Dina noted that the most recent Phase III data are "highly predictive" of the benefit Heplisav could provide those latter kidney disease groups.

In terms of the product's eventual commercialization, he said Dynavax might be able to handle certain niche markets in the U.S. but likely would look to partners for larger audiences and those abroad.

Elsewhere in the company's clinical pipeline is Tolamba, a ragweed allergy immunotherapeutic in a large, late-stage safety and efficacy trial and a supportive study in ragweed-allergic children, as well as a therapy for non-Hodgkin's lymphoma in a Phase II combination trial with Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.).