The US Food and Drug Administration (FDA) has declined to approve a supplemental biologics licence application (sBLA) for Dynavax Technologies’ recombinant hepatitis B vaccine, Heplisav-B.
The agency cited insufficient efficacy and safety data due to the “destruction of data source documents by a third-party clinical trial site operator for approximately half of the subjects enrolled in the trial”. The company did not disclose additional details regarding the destruction of trial documents.
The complete response letter (CRL) issued by the US FDA also went on to state that the “total number of subjects in the single-arm HBV-24 study was deemed to be insufficient to evaluate the safety of the four-dose regimen”.
The sBLA was based on clinical immunogenicity and safety data from the open-label, single-arm Phase I trial (NCT03934736). The study enrolled 119 participants with end-stage renal disease who were undergoing haemodialysis. The sBLA also included data from five other clinical trials for the Heplisav-B vaccine in patients with either chronic kidney disease or undergoing haemodialysis.
Dynavax is no stranger to receiving FDA rejections. The agency rejected Heplisav-B twice due to safety concerns - in 2013 and 2016 - before granting approval for preventing hepatitis B infection in adults in 2017.
The company’s chief medical officer Rob Janssen said: "We remain confident in the data generated to support HEPLISAV-B vaccination for adult haemodialysis patients. All key data collected in HBV-24 were verified against original source documents during the conduct of the trial."
Adding that the company will request a meeting with the FDA to “evaluate options” for additional data needed to support the label expansion for the Heplisav-B vaccine.
Heplisav-B, which is Dynavax’s only marketed vaccine, generated $43.5m in sales in Q1 2024, as per the company’s financials. GlobalData expects the vaccine sales to increase, with the vaccine raking in $700m in 2030.
GlobalData is the parent company of Pharmaceutical Technology.
Other vaccines in Dynavax’s investigational pipeline include Z-1018, a shingles vaccine, CpG 1018, a plague vaccine being developed in collaboration with the US Department of Defense; and Tdap, a triple immunisation vaccine against tetanus, diphtheria, and pertussis. The company plans to start a Phase I/II trial for the shingles vaccine in Q2. The plague vaccine is being evaluated in a Phase II trial (NCT05506969), with topline data expected in Q4 this year.
