The Vaccines and Related Biological Products board voted its confidence in the immunogenicity of Heplisav by a 13 – 1 vote; however, the committee said in an 8 – 5 decision, with one abstention, that it could not recommend the vaccine for approval to the FDA due to insufficient clinical safety data, especially in certain minority groups.
A theoretical concern exists that vaccines containing adjuvants (pharmacological agents added to enhance seroprotection) might induce autoimmune diseases, such as multiple sclerosis. Dynavax’s drug contains the same Hep-B surface proteins (antigen) as currently marketed HBV vaccines. What has some panel members worried, however, is that Heplisav enjoins a first-in-class adjuvant, which activates immune responses by specifically targeting Toll-like Receptor 9 (TLR-9), found on a specialized subset of immune cells.
However, briefing documents posted by the regulatory agency failed to demonstrate a mechanistic link between the company’s TLR-9 agonist and autoimmune response: Pooled results from two pivotal late-stage trials demonstrated the relative risk of developing a serious adverse event in patients treated with Heplisav was no greater than the group injected with the comparator vaccine Engerix-B, marketed by GlaxoSmithKline (GSK).
The risk of African-Americans contracting HBV is three times greater than that of whites. Committee chair Robert Daum, MD, expressed concern “that there’s not enough data from different ethnic groups to be sure the immunogenetic response [of heplisav] is adequate.”
On average, the ethnicities in the two phase-3 trials containing 4,800 participants were White (87.8%); Black (8.8%); and Hispanic (4.3%). However, it’s important to remember that last year blacks and those of Hispanic or Latino origin comprised only 13.1% and 16.7% of the U.S. population, according to U.S. Census Bureau data.
The Advisory Committee did not vote against the approval of the vaccine.
The Advisory Committee voted 8 to 5 that the safety data is insufficient. So there were 5 members that voted clearly for the approval. From the 8 members that voted against the safety data, there were some that voted that a further test could be made POS-approval. I do not know the exact number who voted for that, but I remember to see at least 2 of them. If from 8 members, 2 voted against but accept a POS-approval test, that means that 5+2=7 member are for the approval of the vaccine even if a test is further necessary. That would mean that at maximum 8-2=6 members requested tests pre-approval. In other words the result of the voting was at least 7 for the approval and at maximum 6 against the approval.
#1. "[A]re they worried about safety?" Yes, safety. That is what FDA said. Not complicated.
#2. "What could possibly do wrong?" - 1:30,000 or greater chance of an adverse event.
#3. Bottom Line: FDA wants more data to cover their butts in case an ultra-rare 1:30,000 chance of an adverse event occurs - it's a vaccine afterall. Realize, vaccines are some of the safest, if not THE safest, drugs on the planet. The fact that FDA settled on a 8,000 patient study can only demonstrate confidence in the safety profile. Read the FDA's AdComm docs.