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HEPLISAV-B vaccine safe, effective against HBV in patients with type 2 diabetes
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Adults with type 2 diabetes, who are more susceptible to hepatitis B virus infection than individuals without diabetes, had significantly higher rates of protection against the virus after receiving two doses of the investigational HEPLISAV-B vaccine compared with three doses of a currently licensed vaccine with a similar safety profile, according to preliminary results of a phase 3 trial.
The CDC estimates that people aged 23 to 59 years with diabetes are twice as likely to develop acute HBV compared with those without diabetes, according to a press release. The agency recommends that all adults aged 19 to 59 years be vaccinated against hepatitis B soon after their diabetes diagnosis. Those aged 60 years and older may be vaccinated depending on their risk for infection and probability of having a sufficient immune response, the release said.
Robert Janssen
“The hepatitis B virus [HBV] can spread easily through contact with contaminated medical equipment, such as blood glucose monitors, posing a serious health risk to people living with diabetes,” Robert Janssen, MD, chief medical officer for Dynavax Technologies, said in the release. “Results of this study show that, with two doses over 1 month, HEPLISAV-B provided a significantly higher rate of seroprotection in participants with type 2 diabetes than an existing hepatitis B vaccine.”
HEPLISAV-B is a recombinant vaccine that contains 20 µg rHBsAg and 3,000 µg of adjuvant 1018, a toll-like receptor 9 agonist. During the HBV-23 trial, Sam Jackson, MD, investigator for Dynavax, and colleagues compared the safety and noninferiority of the investigational vaccine at week 28 to Engerix-B (GlaxoSmithKline).
Among more than 8,000 adults included in the analysis, 1,144 had type 2 diabetes. Two-thirds of the diabetes cohort had the condition for at least 5 years. The participants were randomly assigned 2:1 to receive two doses of HEPLISAV-B at baseline and week 4, or three doses of Engerix at baseline and weeks 4 and 24.
The proportion of patients with protection against HBV, defined as anti-HBs of 10 mIU/mL or greater, was 90% (95% CI, 87.4%-92.2%) in participants who received HEPLISAV-B vs. 65.1% (95% CI, 59.6%-70.3%) in those assigned Engerix-B (difference, 24.9%; 95% CI, 19.3%-30.7%). Statistically significant differences favoring HEPLISAV-B were greater in participants aged 60 to 70 years (85.8% vs. 58.5%) and those with a BMI of at least 30 (89.5% vs. 61.4%), according to the release.
As previously reported, the seroprotection rate in the total cohort among participants who were vaccinated with HEPLISAV-B was 95.4% vs. 81.3% with Engerix (difference, 14.2%; 95% CI, 12.5-15.9). 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, and immune-mediated adverse events evaluated by an independent Safety Evaluation and Adjudication Committee 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.
The HBV-23 trial is the third phase 3 trial to evaluate 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. 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 a company press release, Dynavax announced that the FDA has established Dec. 15 as the prescription drug user fee act action date for the biologics license application for HEPLISAV-B.
References:
Jackson S, et al. Poster 139-LB. Presented at: Annual Scientific Sessions of the American Diabetes Association; June 10-14, 2016; New Orleans.
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.
Perspective
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William Schaffner, MD
This is a study of a still unlicensed, but new, hepatitis B vaccine. It was a study conducted in people with type 2 diabetes who were aged 18 to 70 years. It is a recombinant hepatitis B vaccine surface antigen, and it has a toll-like receptor 9 associated with it as an adjuvant, so it is different than the two currently licensed hepatitis B vaccines.
For several years now, the CDC has recommended that people with diabetes be vaccinated against hepatitis B as soon as possible after their diagnosis is established. Everyone up to age 60 years and beyond should consider it depending upon the circumstances of their individual patient. The reason for this is that people with diabetes have two and a half times the frequency of getting infected with hepatitis B as do their nondiabetic counterparts, controlled for by age, race and sex. That is a substantial increase.
Although the CDC has made this recommendation, it has been implemented modestly. Only about 20% to 30% of people with diabetes appear to have been vaccinated and that is less than optimal. One of the reasons that contributes to this is that this recommendation still is not widely known among providers who care for people with diabetes or among diabetic patients. The patients are not asking for it because they are unaware of it.
This is a two-dose vaccine, as opposed to the three-dose vaccine that is currently the standard with the two currently licensed products. Those three doses make it more difficult to completely immunize patients because sometimes the medical record system does not prompt you to remember. You have to give it at time zero, 1 month, and then 1 year from then. And then, some patients do not come back for their immunizations, so that is another reason why people are not optimally immunized.
The results were striking. Patients with diabetes had a 90% seroconversion rate, whereas people who were immunized with a comparator, one of the currently available vaccines, only had a 65.1% seroconversion rate. If you look at it by age, particularly older persons with diabetes, aged 60 to 70 years, the difference was 85.8% vs. 58.5%. If you look at the patients with diabetes who were obese, it was 89.5% vs. 61.4%.
This new vaccine performed in a distinctly superior fashion to the conventional vaccine. When the vaccine becomes licensed, this information will become more widely known to providers and to patients. It will enhance our capacity to provide this protection to our many patients in this country with diabetes. This is a preventive health goal that will be enhanced when this vaccine is licensed by the FDA, which we anticipate might be sometime this year.
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