Type of information: Product launch
Product name: Heplisav-B®
Compound: hepatitis B vaccine
Therapeutic area: Infectious diseases
- vaccine. Heplisav-B® combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist to enhance the immune response. In Phase 3 trials, Heplisav-B® showed higher and earlier protection with fewer doses than a currently licensed hepatitis B vaccine. The most frequently reported local reaction was injection site pain. The most common systemic reactions were fatigue, headache and malaise, all of which were similar to an existing vaccine. Dynavax has worldwide commercial rights to Heplisav-B®.
Company: Dynavax (USA - CA)
Disease: immunization against hepatitis B
- • On January 8, 2018, Dynavax Technologies announced that Heplisav-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted] is now available in the United States for the prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. Heplisav-B® is the first new hepatitis B vaccine in the United States in more than 25 years and the only two-dose hepatitis B vaccine for adults. Heplisav-B® can now be ordered through a network of distributors, which will broaden over the next few weeks. The Wholesale Acquisition Cost (WAC) for Heplisav-B® of $115 per dose, or $230 per regimen, reflects the value Heplisav-B® brings to the healthcare system. Dynavax is currently working with an extensive network of group purchasing organizations and government entities to ensure all patients have access to Heplisav-B®.
- Dynavax has begun activities to support broad reimbursement of Heplisav-B® by insurance plans. Importantly, the American Medical Associationhas published a new and active Current Procedural Terminology (CPT) code for a two-dose adult hepatitis B vaccine, which was created to accommodate Heplisav-B®'s two-dose, one-month schedule. A majority of plans currently have this unique code loaded into their claims processing systems. Some plans will require recommendation from the CDC's Advisory Committee on Immunization Practices (ACIP) prior to covering Heplisav-B®-B. The next ACIP meeting is scheduled for February 21-22, 2018. Proactive payer outreach is currently ongoing, and will include updated ACIP information specific to HEPLISAV-B as it becomes available. Dynavax has staged the deployment of its field sales team to coincide with the upcoming ACIP meeting.
• On November 9, 2017, Dynavax Technologies announced that the FDA) has approved Heplisav-B® for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. The approval of Heplisav-B® was based on data from three Phase 3 non-inferiority trials of nearly 10,000 adult participants who received Heplisav-B®. The pivotal studies compared Heplisav-B® administered in two doses over one month to Engerix-B administered in three doses over a six-month schedule. Results from the largest Phase 3 trial, which included 6,665 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 three 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%). Dynavax expects to commercially launch Heplisav-B® in the United States in the first quarter of 2018. In preparation for launch, Dynavax has been building commercial infrastructure and optimizing manufacturing processes to meet anticipated demand.
• On August 3, 2017, Dynavax Technologies announced that the FDA has requested more detailed information about the company's proposed post-marketing study for Heplisav-B® [Hepatitis B Vaccine, Recombinant (Adjuvanted)] based on feedback received from the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) during a meeting on July 28, 2017. The Advisory Committee voted 12 to 1 (with 3 abstentions) that the safety data for Heplisav-B® support licensure for active immunization against hepatitis B infection in adults 18 years of age and older while also commenting on the design of Dynavax's proposed post-marketing study for Heplisav-B®. Dynavax and the FDA have discussed the outcome of the VRBPAC meeting and have agreed that due to the feedback provided and the proximity to the scheduled Prescription Drug User Fee Act (PDUFA) date of August 10, 2017, more time is required to finalize key details of the post-marketing study.
- As indicated in the FDA's request for additional information, and consistent with the discussion regarding myocardial infarction at the VRBPAC meeting, the remaining details to address in the post-marketing study include:
- Timeline for the final protocol submission, study completion and final report submission
- Timeliness of accruing patients into the study
Time points for data review
- Measures to control for potential biases between study arms
- Updated statistical analysis plan
In order to create sufficient time to complete this work under the existing regulatory framework, the response to the information request will trigger a major amendment to the Biologics License Application (BLA). This will provide the FDA and Dynavax up to three months to agree on the post-marketing study prior to an updated PDUFA date (expected to be no later than November 10, 2017). The FDA and Dynavax have both committed to processing this final stage of the review in the most efficient manner possible by maintaining open channels of communication. This timing does not impact the company's plans to launch Heplisav-B® commercially in the United States in early 2018.
• On July 28, 2017, Dynavax announced that the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 12 to 1 that the safety data for Heplisav-B® support licensure for immunization against hepatitis B infection in adults 18 years of age and older. Three members of the panel abstained.
- The Committee provided commentary on the design of Dynavax's proposed post-marketing pharmacovigilance plan for Heplisav-B®. The FDA did not ask this VRBPAC panel to vote on the immunogenicity of Heplisav-B®. A prior VRBPAC panel voted 13 to 1 that the data from Phase 3 clinical trials supports the immunogenicity of Heplisav-B®.
- Heplisav-B® has a Prescription Drug User Fee Act (PDUFA) date of August 10, 2017. If the FDA approves the vaccine, Dynavax will seek a recommendation from the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) during its October 2017 meeting. Dynavax plans to launch the vaccine commercially in the U.S. in early 2018 on its own or through a commercial partner.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE: 2017-11-09
Favourable opinion USA: 2017-07-28
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: