Drug Development

Dynavax takes a big step toward an OK for hep B vaccine, but nagging safety issues remain

Eddie Gray, Dynavax CEO

Will the third time prove the charm for Dynavax?

More than a few analysts are still asking that question after a panel of outside experts formed by the FDA offered a lopsided vote in favor of an approval — with three abstentions for its hep B vaccine Heplisav and only one opposed for safety reasons.

Efficacy was never really in doubt. The data are solid. But there was plenty of fretting about Heplisav’s safety profile, after regulators spotlighted an imbalance of deaths and cardiac events which has never been explained. The internal FDA review last Wednesday forced the stock $DVAX down 10%, but it rocketed up 80% Friday evening after the experts weighed in on ways that the biotech could keep a careful eye on the health of the people taking their vaccine.

Whether the FDA signs off on that and green-lights the vaccine, after posting a solid set of data in comparison with GlaxoSmithKline’s Engerix-B, is now the big question. The agency only rarely bucks its outside experts, and the mandate at the agency now is definitely in favor of approvals over delay.

This program has already been stiff-armed twice at the FDA, following a clinical hold early on in 2008.

RBC’s Matt Eckler is betting that the company and the FDA can square away a plan for pharmacovigilance, allowing an approval by August 10 and a launch next year — whether or not the biotech can land a partner. But there are plenty of unresolved questions regarding the details and how they may influence the commercial reception. He wrote:

Prior to the positive vote, panel members expressed lingering concerns over the MI (myocardial infarction) signal seen in HBV-23, as well as the sufficiency of the proposed design of the post marketing surveillance program. The current proposal from DVAX is to conduct observational electronic medical record review at Kaiser Permanente Northern California to compare 3-point MACE, and pre-specified immune-mediated events, in 20,000 Heplisav-B recipients vs 20,000 persons who receive another hepatitis B vaccine. Based on this design, the first interim analysis is estimated within 12 months following initiation. Notable panel member concerns with the design included the potential for selection against high-risk patients, which would limit the ability to detect a safety signal, as well as the capacity to provide definitive answers within a reasonable time frame. Additionally, panel members expressed the view that full safety data should be in Heplisav’s label, but that such a label may cause physicians to select against using in high-risk patients for whom the unmet medical need is greatest.

Dynavax is betting that the easier dosing regimen will give them an edge in the market over the GSK rival, but there are no sure things in this market.

“The two-dose regimen offers the potential to increase patient compliance, which physicians and advocates agree is essential to preventing more cases of hepatitis B and achieving the public health goal of eradication,” said CEO Eddie Gray in a statement. “We look forward to completing our ongoing discussions with the FDA regarding an appropriate post-marketing commitment as it finalizes its review.”


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RAPS Regulatory Convergence 2017