FDA Issues CRL for Heplisav-B in Adults With ESRD on Hemodialyis


Dynavax plans to meet with the FDA to discuss how the company can provide additional data to support the approval of its 4-dose Heplisav-B regimen and expand protection for adults with end-stage renal disease (ESRD) on hemodialysis.

The FDA has issued a complete response letter (CRL) in response to a supplemental Biologics License Application (sBLA) from Dynavax Technologies Corporation to include a 4-dose Heplisav-B vaccination [Hepatitis B Vaccine (Recombinant), Adjuvanted] regimen for adults with end-stage renal disease (ESRD) on hemodialysis.1 According to the agency, the company’s application did not provide sufficient data to prove the effectiveness or safety for the 4-dose regimen.

FDA logo on website browser / Postmodern Studio - stock.adobe.com

FDA logo on website browser / Postmodern Studio - stock.adobe.com

Although the submitted sBLA demonstrated clinical immunogenicity and safety data from the phase 1 HBV-24 (NCT03934736) study of a 4-dose regimen of Heplisav-B among adult patients with ESRD undergoing hemodialysis, as well as 5 other clinical trials of Heplisav-B in adults with chronic kidney disease or undergoing dialysis, the FDA determined the data to be insufficient. The agency cited the destruction of data source documents by a third-party clinical trial site operator and a too-small study population to effectively evaluate safety as reasons for the CRL.1

About HBV-24

Trial Name: HEPLISAV-B® in Adults With End-Stage Renal Disease (ESRD) Undergoing Hemodialysis

Clinicaltrials.gov Identifier: NCT03934736

Sponsor: Dynavax Technologies Corporation

Summary: This is an open-label, single arm study design to evaluate HEPLISAV-B® in adults with ESRD who are initiating or undergoing hemodialysis.

“We remain confident in the data generated to support Heplisav-B vaccination for adult hemodialysis patients. All key data collected in HBV-4 were verified against original source documents during the conduct of the trial,” said Rob Janssen, MD, chief medical officer of Dynavax in a news release.1

Final immunogenicity data announced in 2021 from HBV-24, which recruited 119 adults undergoing hemodialysis, showed that Heplisav-B demonstrated a seroprotection rate of 89.3% and generated high levels of anti-HBs antibodies.2 Interim safety data released at the same time revealed no safety concerns.

READ MORE: FDA Expands Tenofovir Alafenamide Indication to Treat HBV in Patients as Young as 6

In a news release, Dynavax noted that the CRL only applies to the 4-dose schedule for dialysis patients in the US. The 2-dose Heplisav-B regimen is still approved for adults 18 and older to prevent hepatitis B infection in the US, European Union, and Great Britain, and the October 2023 decision to approve the 4-dose regimen for the adult hemodialysis patient population in Europe remains unchanged.1

Heplisav-B was first approved by the FDA in 2017 for prevention of infection caused by all known subtypes of hepatitis B virus in adults aged 18 years and older. It was the first new hepatitis B vaccine in the United States in more than 2 decades and the only 2-dose hepatitis B vaccine on the market for adults.3

“Heplisav-B is the first FDA-approved product for Dynavax and demonstrates our ability to develop innovative products and progress them from discovery to commercialization,” said Eddie Gray, chief executive officer of Dynavax in a news release published at the time of the vaccine’s approval.3 “We would like to thank the many study participants and clinical trial investigators who contributed to the development of Heplisav-B. We expect that it will become an essential tool in the public health community’s fight to prevent hepatitis B, and we look forward to making Heplisav-B available to clinicians and their adult patients.”

Although there is no cure for hepatitis B, a serious liver infection, it can be effectively prevented through vaccination. Heplisav-B, which combines hepatitis B surface antigen with Dynavax’s proprietary toll-like receptor 9 agonist to fight off the virus, helps stimulate a strong immune response against the condition.

Moving forward, Dynavax plans to meet with the FDA to discuss how to provide additional data to support the approval of its 4-dose Heplisav-B regimen and expand protection for adults on hemodialysis.

“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 4-dose regimen for this vulnerable patient population in the US,” said Janssen.1

READ MORE: Immunization Update Center

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1. Dynavax provides regulatory update on sBLA for four-dose Heplisav-B regimen for adults on hemodialysis in the US. News release. Dynavax. May 14, 2024. Accessed May 14, 2024. https://investors.dynavax.com/news-releases/news-release-details/dynavax-provides-regulatory-update-sbla-four-dose-heplisav-br
2. Dynavax announces final immunogenicity and interim safety results from clinical trial evaluating Heplisav-B in patients undergoing hemodialysis. January 7, 2021. Accessed May 14, 2024. https://investors.dynavax.com/news-releases/news-release-details/dynavax-announces-final-immunogenicity-and-interim-safety
3. Dynavax announces FDA approval of Heplisav-B™ for prevention of hepatitis B in adults. News release. November 9, 2017. Accessed May 14, 2024. https://investors.dynavax.com/news-releases/news-release-details/dynavax-announces-fda-approval-heplisav-btm-prevention-hepatitis
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