Dynavax Technologies Corporation and Merck & Co. announced top-line immunogenicity results from a phase-3 clinical trial comparing Heplisav, an investigational hepatitis B virus (HBV) vaccine, to a currently marketed HBV vaccine, Engerix-B. The study achieved its primary endpoint. Heplisav is being jointly developed by Dynavax and Merck for use in adults and in patients with end stage renal disease.
This study, called PHAST (phase-3 HeplisAv short-regimen trial), evaluated a two-dose regimen of Heplisav administered at 0 and 1 month compared to a three-dose regimen of Engerix-B administered at 0, 1 and 6 months. The primary endpoint was the proportion of subjects who developed protective antibodies to hepatitis B after administration. In PHAST, 95.1 per cent of subjects, who received two doses of Heplisav (n=1,819) developed protective antibodies to hepatitis B when measured at 12 weeks versus 81.1 per cent of subjects, who received three doses of Engerix-B(R) (n=608), when measured at 28 weeks. The multi-center study evaluated 2,427 subjects from 11 to 55 years of age in Canada and Germany. Results of additional analyses from this trial will be presented in the future.
As previously disclosed, the US Food and Drug Administration (FDA) placed a clinical hold on the two Investigational New Drug (IND) Applications for Heplisav that is still in effect. In issuing the clinical hold, the FDA requested a review of clinical and preclinical safety data for Heplisav. Additionally, the FDA requested all available information about a single case of Wegener's granulomatosis reported in this phase-3 trial.
Heplisav is based on Dynavax's proprietary immunostimulatory sequence (ISS) that specifically targets Toll-Like Receptor 9 (TLR9) to stimulate an innate immune response. Heplisav combines ISS with HBV surface antigen (HBsAg) and is designed to enhance the speed of protection.
Dynavax Technologies Corporation discovers, develops, and intends to commercialize innovative TLR9 agonist-based products to treat and prevent infectious diseases, allergy, cancer, and chronic inflammatory diseases using versatile, proprietary approaches that alter immune system responses in highly specific ways.