HEPLISAV-B Rx

The immunogenicity of Heplisav-B was assessed in comparison with a licensed hepatitis B vaccine (Engerix-B) in 3 randomized, active controlled, observer-blinded, multi-center Phase 3 clinical trials of adults. Heplisav-B was given as a 2-dose regimen at 0 and 1 months followed by saline placebo at 6 months. Engerix-B was given at 0, 1, and 6 months.

The trials compared the seroprotection rates (% with antibody concentration ≥10 mIU/mL) induced by Heplisav-B and Engerix-B. Noninferiority was met if the lower bound of the 95% confidence interval of the difference in seroprotection rates (Heplisav-B minus Engerix-B) was greater than -10%.

Study 1 (Seroprotection in Adults 18-55 Years of Age)

• In Study 1, the immunogenicity population comprised of participants who received Heplisav-B (n=1511) and those who received Engerix-B (n=521). The mean age was 40 years for both groups. The primary analysis compared the seroprotection rate at Week 12 for Heplisav-B with that at Week 28 for Engerix-B. Non-inferiority of the seroprotection rate induced by Heplisav-B compared to Engerix-B was demonstrated as 95% (95% CI, 93.9-96.1) and 81.3% (95% CI, 77.8-84.6), respectively. The difference in seroprotection rates was 13.7% (95% CI, 10.4-17.5).

Study 2 (Seroprotection in Adults 40-70 Years of Age)

• In Study 2, the immunogenicity population comprised of patients who received Heplisav-B (n=1121) and those who received Engerix-B (n=353). The mean age was 54 years for both groups. The primary analysis compared the seroprotection rate at Week 12 for Heplisav-B with that at Week 32 for Engerix-B. Non-inferiority of the seroprotection rate induced by Heplisav-B compared to Engerix-B was demonstrated as 90.1% (95% CI, 88.2-91.8) and 70.5% (95% CI, 65.5-75.2), respectively. The difference in seroprotection rates was 19.6% (95% CI, 14.7-24.8).

Study 3 (Seroprotection in Adults 18-70 Years of Age, Including those with Type 2 Diabetes Mellitus)

• In Study 3, the immunogenicity population comprised of patients who received Heplisav-B (n=4537) and those who received Engerix-B (n=2289). The mean age was 51 years and 14% of patients had type 2 diabetes mellitus (defined as having a clinical diagnosis of type 2 diabetes and taking at least an oral or non-insulin injectable hypoglycemic agent and/or insulin).
• The primary analysis compared the seroprotection rate at Week 28 for Heplisav-B (n= 640) with that at Week 28 for Engerix-B (n= 321) in patients with type 2 diabetes mellitus. Non-inferiority of the seroprotection rate induced by Heplisav-B compared to Engerix-B was demonstrated as 90.0% (95% CI, 87.4-92.2) and 65.1% (95% CI, 59.6-70.3), respectively. The difference in seroprotection rates was 24.9% (95% CI, 19.3-30.7).
• A secondary analysis compared the seroprotection rate at Week 24 for Heplisav-B with that at Week 28 for Engerix-B in the total study population. Non-inferiority of the seroprotection rate induced by Heplisav-B compared to Engerix-B was demonstrated as 95.4% (95% CI, 94.8-96.0) and 81.3% (95% CI, 79.6-82.8), respectively. The difference in seroprotection rates was 14.2% (95% CI, 12.5-15.9).
• Another secondary analysis compared the seroprotection rate at Week 24 for Heplisav-B with that at Week 28 for Engerix-B, by age group. For each age stratum non-inferiority of the seroprotection rate induced by Heplisav-B compared to Engerix-B was demonstrated in the following:

• • Age 18-29:  
    • Heplisav-B: 100.0% (95% CI, 97.9-100.0); Engerix-B: 93.9% (95% CI, 87.3-97.7); Difference in SPRs: 6.1% (95% CI, 2.8-12.6)
  • Age 30-39:  
    • Heplisav-B: 98.9% (95% CI, 97.7-99.6); Engerix-B: 92.0% (95% CI, 88.5-94.7); Difference in SPRs: 6.9% (95% CI, 4.2-10.4)
  • Age 40-49:  
    • Heplisav-B: 97.2% (95% CI, 96.0-98.2); Engerix-B: 84.2% (95% CI, 80.7-87.2); Difference in SPRs: 13.1% (95% CI, 9.9-16.6)
  • Age 50-59:  
    • Heplisav-B: 95.2% (95% CI, 94.0-96.3); Engerix-B: 79.7% (95% CI, 76.6-82.5); Difference in SPRs: 15.5% (95% CI, 12.6-18.7)
  • Age 60-70:  
    • Heplisav-B: 91.6% (95% CI, 89.9-93.1); Engerix-B: 72.6% (95% CI, 68.8-76.2); Difference in SPRs: 19.0% (95% CI, 15.2-23.0)