WASHINGTON -- An FDA advisory committee voted 13-1 in support of the efficacy of a hepatitis B vaccine on Thursday but questioned its safety and lack of information on its effects among certain minorities.
The Vaccines and Related Biologics Advisory Committee voted 5-8, with one abstention, against the safety of Heplisav in adults 18 to 70.
The committee questioned Dynavax, the manufacturer of Heplisav, about the representation of specific populations, including Asians, blacks, and Hispanics.
"Several committee members felt uncomfortable that a representative pool of all Americans was not studied, yet they were asked to vote on suggesting approval to the FDA," according to a summary of the meeting provided to 鶹ý by the FDA. "Some felt the company needed to go back and get more immunogenic data sets in other racial groups in order to make a responsible decision on safety and effectiveness of the vaccine in light of the fact that it contains an adjuvant."
Heplisav combines hepatitis B surface antigen produced in yeast cells with a novel agonist to enhance the immune response. Two doses are administered 1 month apart.
A study of nearly 4,000 patients found that two doses of Heplisav was non-inferior to three doses of GlaxoSmithKline's hepatitis B vaccine Engerix-B, used as the active comparator drug in trials. Efficacy was measured by adequate hepatitis B antibody concentration.
"At least 90% of healthy adult subjects maintained seroprotective antibody levels against hepatitis B at 48 weeks after two doses," the FDA noted in briefing documents released in advance of Thursday's meeting. "Subgroup analyses did not reveal clinically significant differences between antibody responses in younger and older subjects, or between males and females."
Safety was evaluated in more than 5,800 adults up to 28 weeks after injection and up to a year in one pivotal study.
Most adverse events were mild, localized reactions that didn't differ significantly from the comparator Engerix-B. FDA reviews also found no clinically significant differences in safety between Heplisav and Engerix-B.
"The overall safety evaluation across studies did not reveal significant imbalances in rates of clinically important adverse events," the briefing documents said.
Some panelists wanted longer studies and more data on adverse events, according to the FDA's report of the panel meeting. Others wanted more data on the populations at greatest risk for hepatitis B.
Committee members also asked the FDA for an ongoing analysis of the diseases that appeared in patients in the trial to see if there's any causal relationship.
While there are two hepatitis B vaccines already on the market, as well as one that combines hepatitis B and A, all require three doses given up to a year between the first and last. Heplisav is only two doses given 1 month apart.
U.S. prevalence of hepatitis B remains high at around 800,000 to 1.4 million, the FDA said, with between 2,000 and 4,000 deaths a year. Infection rates have dropped since 1992, when universal childhood vaccinations were first recommended.
The FDA is expected to make a decision on Heplisav by Feb. 24. The agency isn't obligated to follow the advice of its advisory committee but usually does so.