Autoimmunity / Inflammation

Pipeline :: HEPLISAV

HEPLISAV™ Hepatitis B vaccine

HEPLISAV(TM) is an investigational adult hepatitis B vaccine comprising our first generation 1018 immunostimulatory sequence (1018 ISS) and hepatitis B surface antigen (HBsAg), manufactured in our Dynavax Europe facility in Düsseldorf, Germany. In Phase 3 trials, HEPLISAV demonstrated earlier and higher protection with fewer doses than currently licensed vaccines.

The Biologics License Application (BLA) for HEPLISAV was accepted for review by the U.S. Food and Drug Administration (“FDA”) in June 2012, with an indication for immunization against infection caused by all known subtypes of hepatitis B virus in adults 18 through 70 years of age. On February 25, 2013, we received a complete response letter (“CRL”) from the U.S. Food and Drug Administration (“FDA”). Following extensive discussions with the FDA, we finalized the design of an additional clinical study of HEPLISAV that is intended to provide a sufficiently-sized safety database for the FDA to complete its review of our BLA and make a final determination regarding the safety and immunogenicity of the product. This study is a Phase 3, observer-blinded, randomized, active-controlled, multicenter trial of the safety and immunogenicity of HEPLISAV compared with Engerix-B® in adults 18 to 70 years of age. The study will include 5,500 HEPLISAV subjects and 2,750 Engerix-B subjects, stratified by age and diabetes diagnosis. HEPLISAV subjects will receive two doses at 0 and 1 month, while Engerix-B subjects will receive three doses at 0, 1 and 6 months.

The primary objectives of the study will be: (1) to evaluate the overall safety of HEPLISAV with respect to clinically significant adverse events and (2) to demonstrate the noninferiority of the peak seroprotection rate (“SPR”) induced by HEPLISAV versus Engerix-B in subjects with type 2 diabetes mellitus. All HEPLISAV subjects will be evaluated for safety for one year following the second dose, all potential autoimmune events will be adjudicated by a Safety Evaluation and Adjudication Committee and safety will be monitored by a Data and Safety Monitoring Board. The study was initiated in April 2014 and subject visits are expected to conclude by the end of 2015.

Additionally, the Marketing Authority Authorization (MAA) filing for HEPLISAV was accepted by the European Medicines Agency (EMA) in August 2012, with an indication for immunization against infection caused by all known subtypes of hepatitis B virus in adults 18 through 70 years of age and for patients with chronic kidney disease. We announced on February 18, 2014 that we had withdrawn the MAA filing for HEPLISAV. The Day 180 List of Outstanding Issues provided by the EMA indicated that the HEPLISAV safety database supporting the MAA was considered to be too small to rule out a risk of less common serious adverse events.  We chose to withdraw the application because the required timeframe for response under the MAA procedure was not long enough to permit the collection of the necessary clinical data. We expect the Phase 3 study initiated in the U.S. will provide additional data to support the safety of HEPLISAV.

Clinical Results

Over 4,800 individuals have been vaccinated with HEPLISAV to date.

In 2011, we reported topline results from our Phase 3 trial (HBV-16), which demonstrated non-inferiority, superiority and the safety of HEPLISAV. The study evaluated a two-dose regimen of HEPLISAV administered at 0 and 1 month, compared to a three-dose regimen of Engerix-B (the commercially available vaccine) administered at 0, 1 and 6 months. The trial studied 2,449 healthy adults 40 to 70 years of age, randomized to HEPLISAV or Engerix-B in a 4:1 ratio. We also reported immunogenicity data from the HBV-16 trial for subpopulations known to be hypo-responsive to currently licensed hepatitis B vaccines (males, obese, and smokers) as well as a diabetic subset analysis from the trial.

Commercial Opportunity

Hepatitis B can be a chronic disease that may lead to cirrhosis of the liver, hepatocellular carcinoma and death. There is no cure for hepatitis B, and disease prevention through effective vaccines is critical to reducing the spread of the disease. Available hepatitis B vaccines for adults have several limitations, including:

  • Slow onset of protection—the current regimen for adults is usually 3 doses given over 6 months to provide seroprotection of approximately 30%, 75%, and 90% after the first, second, and third doses respectively;
  • Poor protection in populations that are hypo-responders—current vaccines provide a lower seroprotection rate for persons over 40 years of age including males, obese, smokers and diabetics, and immunocompromised persons, such as chronic kidney disease and patients on dialysis; and
  • Poor compliance— in certain settings only 30% of people receive all 3 doses.

HEPLISAV is designed to address the limitations of currently licensed vaccines by providing higher seroprotection rates earlier with fewer doses.

We estimate the worldwide market for adult hepatitis B vaccines at approximately $680 million annually. This market is primarily comprised of GlaxoSmithKline’s Engerix-B and Twinrix as well as Merck’s Recombivax-HB. Key market segments, which are persons considered to be at high risk for hepatitis B, include chronic kidney disease patients, people with multiple sexual partners or injection drug use, healthcare workers and first responders, travelers, and chronic liver disease patients.

We intend to focus our initial commercialization efforts on the US market. Currently, the US market for adult hepatitis B vaccines is approximately $270 million annually.  In late 2012 the Advisory Committee on Immunization Practices (“ACIP”) updated their recommendation for adults who should be vaccinated against hepatitis B to include people with diabetes mellitus (type 1 and type 2). According to the Centers for Disease Control and Prevention (“CDC”) there are 20 million adults diagnosed with diabetes and another 1.5 million new cases diagnosed each year. This population represents a significant increase in the number of adults recommended for vaccination against hepatitis B in the US.


Dynavax has worldwide commercial rights to HEPLISAV.


HEPLISAV is a trademark of Dynavax Technologies Corporation