Hepatitis B Vaccine Authorized in Great Britain

This past week, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization in Great Britain for Heplisav B (Hepatitis B Vaccine (Recombinant), Adjuvanted) for the active immunization against hepatitis B virus infection (HBV) caused by all known subtypes of hepatitis B virus in adults 18 years of age and older. The approval was based on the positive benefit-risk for Heplisav B as demonstrated by the safety and immunogenicity results of three phase 3 clinical trials.

"Hepatitis B is a highly infectious and potentially deadly virus with increasing infection rates, and over 250 million people infected worldwide. Thankfully, it can be prevented with effective vaccination," Dynavax CEO Ryan Spencer said in a statement. “This approval highlights the capabilities and continued successful execution of the organization."

FDA Approval
The Heplisav B vaccine was FDA approved in the United States in November 2017. The approval was based from data in three phase 3 non-inferiority trials of nearly 10,000 adult participants who received the Dynavax vaccine. The studies compared Heplisav B administered in 2 doses over one month to Engerix-B administered in three doses over a six-month schedule.

The Dynavax vaccine combines surface antigen with the company’s proprietary Toll-like Receptor 9 agonist to enhance immune response.

Results from the largest phase 3 trial, which included 6665 participants, showed that Heplisav B demonstrated a statistically significantly higher rate of protection of 95% compared with 81% for Engerix-B. In a subgroup analysis of 961 participants with type 2 diabetes, Heplisav B demonstrated a statistically significantly higher rate of protection of 90% compared to 65% for Engerix-B. Across the clinical trials, the most common local reaction was injection site pain (23% to 39%). The most common systemic reactions were fatigue (11% to 17%) and headache (8% to 17%).

In Feburary of 2018, the CDC’s Advisory Committee on Immunization Practices (ACIP) met and decided to include the Heplisav-B on its list of recommended products for vaccination against hepatitis B virus in adults. As insurance providers and medical institutions take their cues from ACIP, this recommendation was seen as an important step in getting the vaccine closer to patient access.

Vaccine Uptake
When it reached the US market, it became the first two-dose HBV vaccination given 1 month apart. Before Heplisav B's approval, full hepatitis B vaccination required 3 shots administered over a 6 month time period.

In the Dynavax announcement on the Great Britain authorization, the company said HBV immunization was expected to add the additional protective benefit of preventing hepatitis D (HDV), as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

Another potential protective benefit to getting a hepatitis b vaccine is that it is known as an “anti-cancer” vaccine because HBV is the leading cause of liver cancer.

Despite these important benefits to a virus that does not have a clinical cure, it is not being utilized the way it should.

“We are over 40 years since the first plasma-drived hepatitis B vaccine was commercially licensed. And hepatitis B still remains a major public health issue,” H. Nina Kim, MD, MSc, a professor and hepatologist with the University of Washington, said in a recent interview with Contagion at CROI.

During her CROI presentation, she made the point that uptake is lacking. “The fact that we have a number of available vaccines doesn’t necessarily mean that everybody is getting them the way that they’re supposed to,” Kim said. “If you look at a variety of studies that look at uptake among adults who are hepatitis b susceptible, it’s about 25% to 30%, depending on which [study] you look at.”

Next Steps
Dynavax is in the process of commercializing the vaccine in Great Britain. "We are very pleased that Heplisav B has received this latest approval and look forward to continuing ongoing discussions with potential commercial partners for Great Britain,” Spencer stated.