Dynavax Technologies Corporation, a clinical-stage biopharmaceutical company, discovers and develops novel products to prevent and treat infectious and inflammatory diseases, has reported the final data from a pivotal phase III trial in patients with chronic kidney disease (CKD) demonstrating early seroprotection and the durability of the immune response to Heplisav compared to Engerix-B. In October 2011, Dynavax reported that the superiority endpoint had been met in this trial.
The trial included 516 patients 18-75 years of age with CKD (stage 3b or higher) in the US, Canada and Germany who received 3 doses of Heplisav at 0, 1 and 6 months or 4 double doses of Engerix-B at 0, 1, 2 and 6 months (8 doses total).
Analysis of the final data demonstrated that:
Heplisav provided seroprotection to 90% of patients compared to 82% for Engerix-B (P=0.01) at the primary endpoint (7 months), 1 month after the 3rd dose of Heplisav and the 8th dose of Engerix-B. This result demonstrated the previously reported superiority of Heplisav seroprotection over Engerix-B.
Heplisav provided seroprotection to more than twice as many patients (Heplisav: 48 per cent; Engerix-B: 20 per cent) at 2 months, 1 month after the 2nd dose of Heplisav and the 4th dose of Engerix-B. This result confirmed the earlier seroprotection of Heplisav in this population.
The geometric mean concentration (GMC) of antibody, which is commonly used to predict the duration of protection in patients with CKD, was approximately four-fold higher in the Heplisav group compared to the Engerix-B group. At Week 28, the GMC for Heplisav was 448 mIU/mL compared to the Engerix-B GMC of 109 mIU/mL. At one year, six months after completing the 3-dose regimen of Heplisav, the GMC was 121 mIU/mL compared to a GMC of 38 mIU/mL six months after completing the 8-dose regimen of Engerix-B.
In a separate trial, in CKD non-responder patients on hemodialysis who had failed to develop seroprotection after two or more previous vaccination series with the licensed vaccines, new data showed a higher seroprotection rate for Heplisav compared to each of Fendrix and Engerix-B.
Heplisav is a trademark of Dynavax, and Fendrix and Engerix-B are registered trademarks of GlaxoSmithKline.
In this study of 119 patients in Germany, the immune responses were compared 4 weeks after a single booster dose of Heplisav or Fendrix or two booster doses of Engerix-B. Data from this booster study showed that Heplisav provided seroprotection to 44 per cent of patients (17/39) compared to 31 per cent (13/42) for Fendrix and 21 per cent (8/38) for Engerix-B.
Dynavax president and chief medical officer, Tyler Martin, MD, said, “These results add to the growing body of evidence of Heplisav's advantages. Patients with CKD are difficult to protect with current HBV vaccines, requiring 8 doses of Engerix rather than 3 doses for healthy adults. The pivotal CKD trial demonstrated the same profile as our healthy adult trials: earlier onset of seroprotection, higher peak seroprotection and improved duration. In addition, the results from the booster trial suggest Heplisav should be the preferred vaccine in this very difficult to protect population, which represents a substantial proportion of patients on hemodialysis.”
Dynavax plans to submit a US Biologics License Application (BLA) for Heplisav by the middle of May for an indication in healthy adults 18-70 years of age for a 2-dose vaccination regimen at 0 and 1 month. A supplemental BLA with an indication and 3-dose primary vaccination regimen for patients with CKD will be filed when the initial BLA is approved.
The Advisory Committee on Immunization Practices (ACIP) and other public health authorities recommend vaccination for all persons with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis and home dialysis patients. Specific regimens or formulations are recommended for both of the currently available hepatitis B vaccines due to the hypo-responsiveness of CKD patients. For immunocompromised persons, including dialysis patients, it is also recommended that additional vaccine be administered as needed to retain seroprotective levels of antibody against hepatitis B.
Heplisav an investigational adult hepatitis B vaccine. In phase III trials, Heplisav demonstrated higher and earlier protection with fewer doses than currently licensed vaccines. Dynavax has worldwide commercial rights to Heplisav. It combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist to enhance the immune response.