An FDA advisory committee voted 12-1, with three abstentions, in support of the safety of Heplisav-B, a hepatitis B vaccine for adults ages 18 and older.
The agency asked the Vaccines and Related Biological Products Advisory Committee whether they were satisfied specifically with the safety data because pivotal trials had shown there were numerically more deaths and serious heart problems in those given Heplisav-B than in those given a rival product Engerix-B -- and these concerns were heightened in high-risk populations.
Indeed, an FDA advisory committee in 2012 voted in favor of the vaccine's efficacy but against its safety in adults.
In response to these findings, Dynavax proposed a large observational post-marketing vaccine surveillance study to be conducted at Kaiser Permanente with 20,000 patients receiving Heplisav-B and 20,000 receiving an alternative hepatitis B vaccine.
Panelists pointed out several holes in that study's design -- though overall, it wasn't enough for them to withhold support for the vaccine.
Meeting chair Kathryn Edwards, MD, of Vanderbilt University, spoke for many in the group when she said she was dismayed by the proposed pharmacovigilance plan and that the company needs to track patient outcomes carefully.
"It needs to be more comprehensive about how patients would be allocated and followed ... and how the vaccine would be distributed," she said.
Karen Kotloff, MD, of the University of Maryland School of Medicine, echoed that sentiment, stating that "if the study was done at multiple centers, there could be faster accrual and quicker answers. It should also be powered for age at MI, and longer term surveillance for autoimmune effects."
Milton Packer, MD, of Baylor University Medical Center, who abstained from the vote, complemented the study design, saying the sponsors "have come up with a brilliant plan for a study which could be a cluster randomization and certain Kaiser clinics would use one vaccine versus another on an elusive basis." The actual assignment could be randomized, with low likelihood of major confounding, he added.
Pamela McInnes, MD, of the National Institutes of Health, who cast the lone dissenting vote, wasn't satisfied with the safety data presented by the sponsor: "The data have been massaged as best can, and they are what they are," she said, adding that the vaccine should be studied further.
The panelists were not asked to vote on whether the drug should be approved or not.
Most participants in the open public hearing favored approval of the vaccine. "Every prevention is another life saved," said Nick Walsh of the Pan American Health Organization. "In order to eliminate hepatitis B as a public health threat, we need vaccination and treatment. A big gap is poor coverage among adults at risk of infection and we believe that a shortened duration with less injections can result in improved coverage."
Manufactured by Dynavax Technologies of Berkeley, Calif., Heplisav-B combines a yeast-derived recombinant hepatitis B virus with a proprietary adjuvant and is administered in two doses over a 1-month period. The vaccine uses a toll-like receptor 9 agonist, compared with current formulations that use alum, in order to enhance B- and T-cell responses to co-administered vaccine antigens.
The vaccine is designed to enhance the body's immune response to the hepatitis B virus, which can lead to cirrhosis of the liver, cancer, and death. To date, more than 10,000 adults have received the vaccine throughout 11 clinical trials.
The FDA is not required to follow the advice of its advisory committees, but it often does.