About 8 months after the FDA rejected Dynavax’s hep B vaccine Heplisav, the biotech is once again under scrutiny at the agency.
And one more time, FDA reviewers are zeroing in on the vaccine’s safety profile as it preps another marketing decision for this long-delayed effort.
Last November the FDA said it wasn’t able to properly assess additional details on the adverse events — particularly an imbalance in the cardiac events that regulators were fretting over. In an internal review ahead of Friday’s panel discussion on Heplisav, regulators say that while it is clear that there is an imbalance in deaths and cardiac events, the number they’re talking about is small and hard to read.
Dynavax’s shares $DVAX dropped 10% in premarket trading as investors pondered a long review document and Dynavax’s chances of winning a green light after being snubbed twice.
From the agency review:
In summary, Heplisav was shown to have a robust immune response in healthy adults 18- 70 years of age in Studies DV2-HBV-10 and-16. Heplisav met pre-specified noninferiority criteria to an active comparator vaccine, Engerix-B, in these two phase 3 clinical trials. Regarding safety, there appear to be imbalances in deaths and SAEs of MI (myocardial infarction) in DV2-HBV-23, and imbalances in AESIs in DV2-HBV-16 and -23 (the studies that prospectively evaluated these events). Numbers and rates of events are low, and the lack of prospectively defined monitoring and evaluation of cardiac events limits the causal interpretation of these observations.
Whatever else you can say about Dynavax, it’s been doggedly persistent in pursuing an approval of Heplisav in the face of repeated safety questions, soldiering on after a clinical hold was dropped on the program in 2008. The biotech aroused some anger among analysts last fall when it revealed the issue on cardiac events for the first time. And it’s likely all up to the panel review on Friday now, notes RBC’s Matthew Eckler:
(W)e anticipate that discussion Friday will focus heavily on new safety data from the latest Phase III trial (HBV-23), specifically the imbalance in cardiac SAEs. Net-net we view the FDA briefing documents as mixed, and fairly neutral, but far from the worst-case scenario for Dynavax. Thus, we think the fate of the BLA hinges on the outcome of Friday’s panel, and the VRBPAC’s willingness to accept some risk with the recommendation for post-marketing pharmacovigilance.
The vaccine gained positive attention, though, as it beat out GSK’s rival Engerix-B in a head-to-head matchup. Dynavax shares were crushed last fall in the requiem, leaving the biotech looking for a partner which has so far not materialized.
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