Heplisav-B approval ‘highly probable’ as FDA Advisory Committee favors Dynavax on third try

An FDA Advisory Committee has cleared Dynavax’s hepatitis B vaccine Heplisav-B, sending it on a positive note before a final decision by the FDA.

Third time’s a charm. After two earlier attempts came up short, an FDA Advisory Committee has favored Dynavax’s hepatitis B candidate Heplisav-B by a vote of 12 to 1, with three abstentions.

Now that the panel has cast its favorable vote for the vaccine’s safety, it’s up to the FDA to consider its final stand.

Heplisav-B development has been a rough road haunted by safety issues, on which the panel discussion July 28 was again focused. However, analysts at RBC Capital, in a note sent to investors, said they “view the vaccine as largely derisked and see ultimate approval as highly probable,” and that the remaining near-time regulatory debate is only around timing of approval.

During the panel discussion last Friday, members again expressed concerns over the safety issue, plus the sufficiency of the proposed design of the postmarketing surveillance program, wrote RBC analyst Matthew Eckler in his note. “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.”

RELATED: With eyes on Glaxo's Engerix-B vaccine, VBI takes hep B candidate into phase 3

Besides the stronger protection rate, the vaccine’s two-dose regimen is delivered in over one month, compared to three doses in six months, and “offers the potential to increase patient compliance,” said Eddie Gray, CEO of Dynavax, in a statement. Gray also said that the company is willing to work with the FDA for an appropriate postmarketing pharmacovigilance program.

Regulators placed a clinical hold on Heplisav-B in 2008 because of an autoimmune adverse event, followed by a complete response letter in 2013 against Dynavax’s first attempt, asking for additional clinical trials to further evaluate the safety profile. The FDA shot down Dyanvax’s application for a second time in 2016, citing an imbalance in cardiac events.

Efficacy was never the problem. The vaccine provides better, 95% vs. 81%, seroprotection against GlaxoSmithKline’s current standard-of-care Engerix-B, according to a head-to-head phase 3. Last time the FDA had convened a panel, the vote was 13 to 1 in support of the shot’s efficacy.

Challenging a product that’s been hogging the market for decades isn’t going to be easy. Based on a possible 2018 launch, Eckler projected “relatively modest trajectory as physicians gain comfort with” the product, with peak U.S. sales of $290 million in 2026. As the search for a partner following the second CRL returned no results, the company said it is prepared to launch the shot on its own.

The next Prescription Drug User Fee Act date falls on Aug. 10, when the FDA must review new drug applications. If Heplisav-B is approved, Dynavax said it would seek a recommendation from the CDC’s Advisory Committee on Immunization Practices during its October 2017 meeting.