Regulatory update on sBLA for four-dose Heplisav-B regimen for adults on hemodialysis in the US

The FDA has issued a Complete Response Letter (CRL) in response to the sBLA, stating that the application did not provide sufficient data to support the full evaluation of effectiveness or safety of a four-dose regimen of Heplisav-B. The CRL has no impact on the approved indication for Heplisav-B. in the U.S., the European Union, and Great Britain, which is for the prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older. The CRL also does not affect the approval decision received from the European Commission in October 2023 for the four-dose Heplisav-B. regimen for the adult hemodialysis population.

The sBLA was comprised of clinical immunogenicity and safety data from the Phase 1 HBV-24 study of a four-dose regimen of Heplisav-B in 119 adults undergoing hemodialysis, as well as five supportive clinical trials of Heplisav-B in adults with chronic kidney disease or undergoing hemodialysis. The CRL stated that the data from HBV-24 were insufficient 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. In addition, the total number of subjects in the single-arm HBV-24 study was deemed to be insufficient to evaluate safety of the four-dose regimen.

"We remain confident in the data generated to support Heplisav-B vaccination for adult hemodialysis patients. All key data collected in HBV-24 were verified against original source documents during the conduct of the trial," said Rob Janssen, M.D., Chief Medical Officer of Dynavax. "We are reviewing the agency's feedback and intend to request a meeting with the FDA to evaluate options for providing additional data to support the four-dose regimen for this vulnerable patient population in the U.S.