Preventing Hepatitis B With Heplisav-B Vaccine

Heplisav-B is a vaccine used to prevent all subtypes of hepatitis B. It was approved by the U.S. Food and Drug Administration (FDA) on November 9, 2017 for use in adults 18 and older.

It is one of three vaccines currently used to prevent infection from the hepatitis B virus (HBV) in the United States. These include Recombivax HB, which was approved by the FDA in 1986, and market leader Engerix-B, which was granted similar approval in 2007. (There is also a third combination vaccine, known as Twinrix, which vaccinates against both hepatitis A and B.)

One of the major benefits of Heplisav-B is that it requires fewer injections over a shorter period of time, a factor which may help people complete the series rather than stopping short.

The approval of Heplisav-B capped a four-year struggle to bring the vaccine to market. The FDA had previously rejected the drug in February 2013 and later in November 2016 due to safety concerns regarding the potential risk of acute myocardial infarction (heart attack) and certain autoimmune diseases.

The vaccine was eventually approved based largely on the fact that it requires two shots delivered one month apart. The other vaccines, by contrast, require three shots separated by one month and then six months.

This was considered important since one of the biggest barriers to HBV vaccination has been adherence. A 2008 study by the Department of Infectious Disease at the University of Florida in Jacksonville reported that, of 707 people eligible for HBV vaccination, only 503 accessed treatment and only 356 completed the three-shot series. Other studies have reported similarly dismal results.

By narrowing the gap between injections, the FDA believes that the benefits of the vaccine far outweigh any potential consequence.

The approval of Heplisav-B was based on data from three clinical trials involving over 14,000 adult participants. The pivotal study compared a two-dose course of Heplisav-B to a three-dose series of Engerix-B. Among the 6,665 participants involved in the study, 95 percent achieved high levels of protection from Heplisav-B (as measured by antibody activity) compared to 81 percent on Engerix-B.

In a second study involving 961 people with type 2 diabetes (considered to be at high risk of hepatitis B), Heplisav-B was reported to provide high-level protection in 90 percent of those given the vaccine versus only 65 percent in those given Engerix-B.

Moreover, Heplisav-B is known to provide protection against all four major serotypes, ten genotypes (A through J), and 40 subgenotypes.

Heplisav-B is delivered by intramuscular injection into the upper deltoid muscle of the shoulder. The vaccine is not a live vaccine (containing live, weakened virus) but instead contains a genetically modified antigen—essentially an avatar for the virus—which does not cause disease but rather stimulates a protective immune response.

After you are given the first 0.5-milliliter (mL) injection, a second would be delivered in six months.

If, for any reason, you are unable to complete the series within that time, speak to your doctor about finalizing the series as soon as possible. It is unlikely you would have to restart the series.

While some people may experience a reaction to the shot, most cases are mild and resolve within a few days. By and large, the reactions, if any, tend to be more profound following the first shot and less so after the second.

The most common symptoms (occurring in over two percent of patients) include:

• Swelling at the injection site - 2.3 percent
• Redness at the injection site - 4.1 percent
• Malaise - 9.2 percent
• Headache - 16.9 percent
• Fatigue - 17.4 percent
• Pain at the injection site - 38.5 percent

Heplisav-B should not be used in persons with a history of severe allergic reactions or those who have had a previous reaction to a hepatitis B vaccine or any of its components, including yeast. Re-exposure could result in a potentially life-threatening, all-body allergic reaction known as anaphylaxis.

To date, there have been no human studies into the effect of Heplisav-B during pregnancy or breastfeeding. However, an animal study reported no adverse events in either pregnant lab rats or their offspring following a 0.3 mL dose of Heplisav-B.

Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer, and death.

According to a report from the U.S. Preventive Services Task Force (USPSTF), anywhere from 700,000 to 2.2. million people are believed to be infected with HBV in the United States. Rates of infections are highest among adults 30 to 49, most whom get infected either through unprotected sex or shared needle use.

There is no cure for hepatitis B, but effective vaccination can prevent the disease. For this reason, the Advisory Committee on Immunization Practices (ACIP) and currently recommends that all children receive their first dose of HBV vaccine at birth and complete the series between six and 18 months. Older children and adolescents who did not receive the HBV vaccine should also be vaccinated.

The Centers for Disease Control and Preventions further recommends that all adults at high risk for HBV be vaccinated. These include:

• Person whose live with or have sex with someone who has hepatitis B
• Sexually active persons who are not in a long-term, mutually monogamous relationship
• Persons seeking testing or treatment for a sexually transmitted infection
• Men who have sex with men
• People living with HIV
• People who share needles, syringes, or other drug paraphernalia
• Healthcare professionals and others at risk of blood exposure
• People with end-stage kidney disease
• People with chronic liver disease
• People with diabetes under the age of 60, started as soon as possible after diagnosis
• International travelers to regions with moderate to high rates of hepatitis B
• Persons who have immigrated from countries with moderate to high rates of hepatitis B or children born to parents who have immigrated from these countries prior to their birth
• Anyone who considers themselves to be at risk

The USPSTF does not currently recommend HBV vaccination for the general adult population as the practice has not been shown to reduce the risk of either liver-related illness or death.

Despite a largely positive reception by public health officials, safety concerns continue to plague the vaccine given its early rejections by the FDA.

The FDA initially rejected the vaccine in 2013 based on one of its components, known as CpG 1018. This is the compound used to boost the vaccine's immune-triggering capabilities and the very one that enables the two-shot series.

According to the FDA response, CpG 1018 was believed to have the potential to trigger certain autoimmune disorders, including thyroid disease. While the early studies showed no statistical difference between Heplisav-B and Engerix-B, the application was denied simply because the size of the study at the time was considered too small.

By the time of the reapplication, 14,238 people had been exposed to the vaccine with only two cases of Hashimoto’s thyroiditis (a form of thyroid disease) and one case of vitiligo reported.

Later, in 2016, the vaccine was also rejected when one study reported a larger than expected number of cardiac events, including heart attacks. In this case, the FDA requested additional information regarding any non-associated factors that could help better explain the results.

Upon review of the additional data, the FDA granted approval. The final trial results reported a 0.1 percent risk of heart attack in people given Heplisav-B versus 0.2 percent given Engerix-B.