Positive results have been reported from HBV-23, a phase 3 trial of the investigational hepatitis B vaccine Heplisav-B (Dynavax Technologies Corporation) compared with a currently marketed vaccine, Engerix-B (hepatitis B vaccine [recombinant], GlaxoSmithKline), in more than 8,000 adults 18 to 70 years of age.
The Heplisav-B cohort received two doses, at zero and one month, and the Engerix-B cohort received three doses, at zero, one, and six months. The study had two co-primary endpoints: the overall safety of Heplisav-B with respect to clinically significant adverse events, and the noninferiority of seroprotection in participants with type-2 diabetes mellitus. Both co-primary endpoints were met.
Results from the safety evaluation included the following:
- An adverse event of special interest (AESI) was experienced by 22 Heplisav-B subjects compared with 11 Engerix-B subjects. All of the events were classified as not related to vaccination.
- Of the 33 AESIs in the study, 21 were judged to be autoimmune events by the independent panel, with 11 reported in participants who received Heplisav-B and 10 reported in participants who received Engerix-B.
- In a secondary safety endpoint, there were no cases of Wegener’s granulomatosis (granulomatosis with polyangiitis) or Tolosa–Hunt syndrome.
- One event in the Heplisav-B arm was coded by a site investigator as a rare autoimmune disease, Takayasu’s arteritis, based solely on a radiological diagnosis. The independent panel of experts concluded that the diagnostic criteria for the initial radiological diagnosis were not met and adjudicated the event as not related to vaccination.
The safety database for Heplisav-B now includes a total of 10,038 participants.
Immunogenicity data from the trial demonstrated that the peak seroprotection rate (SPR) in participants with type-2 diabetes mellitus who received Heplisav-B was 90% compared with 65% for Engerix-B, demonstrating noninferiority and a significantly higher percentage of seroprotection provided by Heplisav-B compared with Engerix-B.
In additional secondary endpoints:
- The peak SPR in the entire Heplisav-B group (95%) was significantly higher than the peak SPR in the Engerix-B group (81%).
- The peak SPR in the Heplisav-B group was significantly higher than the peak SPR in the Engerix-B group in each age decile.
- The peak SPR in the Heplisav-B group was significantly higher than the peak SPR in the Engerix-B group in each prespecified subpopulation analyzed, including by sex, body mass index, and smoking status.
Heplisav-B is an investigational adult hepatitis B vaccine that combines hepatitis B surface antigen with a proprietary Toll-like receptor 9 (TLR9) agonist to enhance the immune response.
Dynavax plans to resubmit the Heplisav-B biologics license application (BLA) at the end of the first quarter of 2016 and anticipates a six-month review by the FDA. In the revised BLA, the company plans to address all issues raised by the FDA in a February 2013 complete response letter (CRL) by submitting the results of the HBV-23 trial, integrated with previous clinical data, and responses to chemistry, manufacturing, and controls (CMC) issues in the CRL.
Source: Dynavax; January 7, 2016.
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