Dynavax’s Heplisav-B passes key regulatory hurdle with FDA Advisory Committee endorsement


In late July, Dynavax received a long-awaited approval from the US Food and Drug Administration's (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC), which voted 12-1 in favour of its investigational vaccine, Heplisav-B (hepatitis B vaccine, recombinant [adjuvanted]).

Despite lingering safety concerns centered on unexplained occurrences of myocardial infarction (MI) in Phase III trials, GlobalData views the latest vote as a victory for Dynavax, which has encountered multiple setbacks in its quest to obtain the FDA’s support for its lead asset.

The committee of outside experts laid the groundwork for an eventual approval by acknowledging that clinical data sufficiently demonstrated the safety of Heplisav-B, which has now been investigated in more than 12,000 patients across five Phase III studies. The latest of these trials, HBV-23, enrolled more than 8,000 participants in response to a 2013 complete response letter that requested additional data be amassed. A final decision on Heplisav-B should be reached by 10 August.

Developed with the goal of protecting nonresponders to currently available hepatitis B vaccines, Heplisav-B contains Dynavax’s proprietary 1018 immunostimulatory sequence (1018 ISS) adjuvant. This is a toll-like receptor 9 (TLR9) agonist that is thought to enhance the vaccine’s immunogenicity by activating the innate immune system. To date, clinical data largely supports this hypothesis; but the adjuvant has proven to be a double-edged sword for Dynavax.

While a two-dose series of Heplisav-B has performed well against a three-dose regimen of GlaxoSmithKline’s (GSK) Engerix-B (hepatitis B vaccine [recombinant]) in pivotal trials, apprehension from the FDA and other regulatory bodies has largely focused on the safety of this novel adjuvant.

In recognition of these concerns, the VRBPAC has only offered its endorsement provided that Dynavax optimise the design of a post-marketing study to confirm the safety of Heplisav-B in at least 20,000 patients within 12 months of its approval and launch.

As a cure for hepatitis B remains elusive, vaccination remains the most effective strategy for reducing the burden of chronic hepatitis B on the healthcare system. While the immunisation of children has achieved resounding success over the past two decades, the protection of adults remains a key unmet medical need. Despite official recommendations from the Centers for Disease Control and Prevention (CDC) calling for the vaccination of all high-risk adults, key opinion leaders (KOL) interviewed by GlobalData cite several factors that have contributed to low vaccine uptake in adults, including poor physician knowledge of adult immunisation recommendations, inadequate adult vaccine reimbursement frameworks, and reduced patient compliance.

According to GlobalData’s primary research, Heplisav-B’s two-dose regimen (administered over one month) represents a crucial advantage over the current standard Engerix-B, which requires three doses over the course of six months. GlobalData anticipates that this improvement will help to eliminate compliance issues specifically related to the six-month dose of the vaccine. Nonetheless, Heplisav-B’s approval will not guarantee its uptake and commercial success, as Dynavax must work with regulators and healthcare providers to overcome the aforementioned barriers to vaccine uptake in the adult population.