Third phase 3 trial shows HEPLISAV-B vaccine safe, effective against HBV

Issue: May 2016

BALTIMORE — Results from the HBV-23 phase 3 trial show that the investigational hepatitis B vaccine HEPLISAV-B provided statistically significant higher rates of protection with fewer doses than a currently licensed vaccine with a similar safety profile. It is the third phase 3 trial to evaluate the vaccine’s safety and noninferiority.

Click on image to enlarge.

“There are 20,000 new infections in the United States with this disease. The vast majority — and I mean the vast majority — of these occur in adults,” Sam Jackson, MD, investigator for Dynavax Technologies, said during his presentation at the Annual Conference on Vaccine Research. “There has been a recent uptick in individuals who use injection drugs.”

According to Jackson, current HBV vaccines have limitations, including the negative effects of age, obesity, smoking and other factors on seroprotection. In addition, some adults have difficulty adhering to a vaccine regimen with three doses over 6 months, which is required of all currently available HBV vaccines.

The HEPLISAV-B recombinant vaccine contains 20 µg rHBsAg and 3,000 µg of the adjuvant 1018 — a toll-like receptor 9 agonist — and is administered in two doses spaced 1 month apart. In the HBV-23 trial, researchers evaluated the overall safety and noninferiority of HEPLISAV-B at week 28 to Engerix-B (GlaxoSmithKline). A co-primary endpoint of the study was to evaluate the noninferiority of the vaccine in patients with type 2 diabetes, but those data will be presented at another scientific conference at a later date, Jackson said.

More than 8,000 adults aged 18 to 70 years were randomly assigned 2:1 to receive HEPLISAV-B or Engerix-B. Participants were stratified by age, study site and diabetes status. Seroprotection was defined in the study as anti-HBs of 10 mIU/mL or greater.

“Demographic and baseline characteristics were very similar across both groups,” Jackson said.

Results indicated that the seroprotection rate was significantly higher in participants who received vaccination with HEPLISAV-B compared with Engerix-B — 95.4% vs. 81.3% (difference, 14.2%; 95% CI, 12.5-15.9). These results were consistent across subpopulations with the exception of Asian participants, although Jackson said this may be due to the relatively few Asian participants enrolled in the study.

Adverse events (46% vs. 46.2%), serious adverse events (6.2% vs. 5.3%) and deaths (0.4% vs. 0.3%) were comparable between the two study arms, Jackson said. Immune-mediated adverse events were evaluated by an independent Safety Evaluation and Adjudication Committee and were found to be unrelated to vaccination with HEPLISAV-B. New onset adverse events of “special interest” — such as alopecia areata, Bell’s palsy, polymyalgia rheumatica and ulcerative colitis — also were evenly distributed across both study arms, according to Jackson.

Jackson emphasized that this was a “real world” trial — the average age of participants was 51 years, almost half were obese, almost one-third were smokers, and 14% had diabetes.

Thus far, there have been three phase 3 trials of HEPLISAV-B. In 2012, an FDA advisory committee determined that the vaccine was effective at preventing infection in adults but its safety had yet to be adequately evaluated to warrant use in the general population. Two years later, Dynavax withdrew its European Marketing Authorization Application for the vaccine after the European Medicines Agency determined that the current safety database was too small to rule out the risk for less common serious adverse events and the required response time was too limited to gather the required clinical data. According to Dynavax, the HBV-23 trial now brings the number of participants in the safety database to 14,238 — 10,038 of whom received HEPLISAV-B and 4,200 of whom received Engerix-B.

In March, the company announced that the FDA has accepted for review the Biologics License Application for HEPLISAV-B.

Robert Janssen

“Consistent with all of our previous trials, these data show that HEPLISAV-B provided higher rates of protection earlier with fewer doses and a similar safety profile,” said Robert Janssen, MD, chief medical officer and vice president of clinical development for Dynavax, said in a press release. “If approved, this vaccine could offer a better way to protect people from a chronic infection that can cause cirrhosis of the liver, cancer or death.” – by John Schoen

Reference:

Jackson S, et al. Abstract S2. Presented at: Annual Conference on Vaccine Research; April 18-20, 2016; Baltimore.

Disclosures: Jackson and Janssen are employed by Dynavax Technologies.