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

News
Article

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

Ready to impress your pharmacy colleagues with the latest drug information, industry trends, and patient care tips? Sign up today for our free Drug Topics newsletter.

References
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
Recent Videos
© 2024 MJH Life Sciences

All rights reserved.