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U.S. Approves New Hepatitis B Vaccine as Public Health Agencies Update Guidelines


On November 9 the U.S. Food and Drug Administration(FDA) approved Heplisav-B, a new vaccine that provides protection against all known subtypes of hepatitis B virus (HBV) with 2 rather than 3 doses, which is expected to reduce the number of people who do not complete the vaccine series.

In related news, the American College of Physicians (ACP) and the Centers for Disease Control and Prevention (CDC) released new guidelines for hepatitis B screening, vaccination, and care.

Hepatitis B is a blood-borne disease of the liver. In the U.S. and Europe it is commonly transmitted through sharing needles to inject drugs or sexual contact. In parts of Asia and Africa it is endemic and often transmitted from mother to child.

Most people infected with HBV as adults are able to clear the virus naturally and only about 10% develop chronic infection; however, among those infected as infants or young children around 90% develop chronic infection. Over years or decades chronic HBV infection can cause severe liver damage including cirrhosis and hepatocellular carcinoma, a type of liver cancer. Hepatitis B can be treated with antiviral drugs but it is seldom cured. The HBV vaccine is now included as a routine infant vaccination in the U.S. and many other countries.

Heplisav-B, developed by Dynavax Technologies, combines hepatitis B surface antigen (HBsAg) with a toll-like receptor 9 (TLR-9) agonist as an adjuvant to enhance immune response. The new vaccine is indicated for people age 18 and older. It is given as 2 doses administered within 1 month. It is expected to become available during the first quarter of 2018.

Heplisav-B is the first new HBV vaccine to be approved in the U.S. in more than 25 years. The existing widely used vaccines, GlaxoSmithKline's Engerix-B and Merck's Recombivax HB, require 3 doses given over the course of 6 months. Experts estimate that nearly half of people who get an initial dose do not complete the full series. A combination HBV and hepatitis A vaccine (Twinrix) is also available.

Approval of Heplisav-B was based on data from 3 Phase 3 clinical trials, which together enrolled nearly 10,000 participants, comparing 2 doses of Heplisav-B versus 3 doses of Engerix-B. In the largest study, Heplisav-B offered significantly greater protection than Engerix-B (95% vs 81%, respectively). People with diabetes are more susceptible to hepatitis B, and Heplisav-B also worked better than Engerix-B for diabetic patients (90% vs 65%, respectively).

Heplisav-B was generally safe and well-tolerated. Across the 3 trials the most common adverse events in both the Heplisav-B and Engerix-B arms were injection site pain(23% to 39%), fatigue (11% to 17%), and headache (8% to 17%).

This month's approval comes after 2 previous rejections as the FDA sought more information on the vaccine's safety and asked for details about post-marketing studies. In the pivotal trials, deaths and serious cardiovascular events such as heart attacks were more common among people who received Heplisav-B, but the overall number of these events was small. The FDA briefing document on Heplisav-B concluded that these findings were likely due to random variation. In July an FDA advisory committee voted 12-1 in favor of the vaccine's safety, with 3 abstentions. Post-marketing studies focused on cardiovascular events and immune-mediated events will be conducted at Kaiser Permanente Northern California.

"Prevention of hepatitis B in adults through vaccination is more important than ever given the increase in the rate of infections,"  William Schaffner of Vanderbilt University Medical Center said in a Dynavax press release. "Too many at-risk adults remain unprotected against this virus. A 2-dose schedule with higher rates of protection, along with other strategies, may help us move closer to the goal of eliminating hepatitis B as a public health problem in the United States."

New Hepatitis B Guidelines

The new ACP and CDC guidelines, published online in Annals of Internal Medicine, call for expanding screening for at-risk adults, increasing hepatitis B vaccination rates, and linking diagnosed individuals to care. Experts estimate that about two-third of people with HBV infection do not know their status.

The recommendations are based on a review of relevant medical literature on hepatitisB vaccination, screening, and linkage to care published from January 2005 (when potent HBV antivirals with low resistance rates became available) through June 2017.

The guidelines recommend HBV vaccination for the following groups:

  • People at risk for percutaneous or mucous exposure to HBV
  • People who inject drugs (current or recent)
  • People at risk for HBV infection due to sexual exposure
  • Gay and bisexual men (men who have sex with men)
  • People who have multiple sex partners
  • People with a history of sexually transmitted infections
  • People who live in the same household as a person with hepatitis B
  • People who have sex with a person with hepatitis B
  • People with chronic liver disease, including hepatitis C or fatty liver disease
  • People with HIV
  • People with end-stage kidney disease, including those receiving hemodialysis
  • Health care and public safety workers at risk for blood exposure
  • Incarcerated individuals
  • People who live at, work at, or regularly visit prisons, jails, drug addiction treatment facilities, or centers for developmentally disabled people
  • Travellers to regions where HBV is endemic
  • Pregnant women who are at risk for HBV infection
  • Any other adult seeking protection from HBV infection

HBV screening is advised for people at high risk for infection, which in addition to the groups above also include the following:

  • People born in countries with an HBV prevalence of 2% or higher
  • People who require immunosuppressive therapy
  • Blood and tissue donors
  • People with elevated alanine aminotransferase (ALT) levels
  • All pregnant women
  • Infants born to mothers with hepatitis B.

The guidelines state that physicians should provide post-test counseling and care for all patients diagnosed with HBV infection or refer them to other appropriate providers. Everyone with chronic hepatitis B should be routinely evaluated for liver cancer. Eligibility for treatment should be determined based on medical history and physical exam results.

"Vaccination of susceptible adults is important to prevent infection and reduce ongoing transmission. Screening in high-risk populations is the first step in the care cascade to identify persons with chronic HBV infection, and vaccination and linkage to care are effective at reducing HBV-associated morbidity and mortality," the guidelines authors write. "Evidence-based strategies that effectively implement this advice are critical to accomplishing the goals of the national hepatitis B elimination plan."



Dynax Technologies. Dynavax Announces FDA Approval of Hepislav-B for Prevention of Hepatitis B in Adults.Press release. November 9, 2011.

American College of Physicians and Centers for Disease Control and Prevention. ACP and CDC issue recommendations for hepatitis B screening, vaccination, and care. Press release. November 20, 2017.

WE Abara, A Qaseem, S Schillie et al. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Annals of Internal Medicine. November 21, 2017.