Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States.

OBJECTIVES: The first 3-antigen hepatitis B vaccine was approved by the United States (US) Food and Drug Administration in November 2021 and was recommended by the Centers for Disease Control and Prevention in 2022. We estimated the cost-effectiveness of this 3-antigen vaccine (PreHevbrio™) relative to the single-antigen vaccine, Engerix-BTM, to prevent hepatitis B virus (HBV) infection among US adults. METHODS: A cost-effectiveness model was developed using a combined decision-tree and Markov structure to follow 100,000 adults over their remaining lifetimes after vaccination with either the 3-antigen or single-antigen vaccine. Outcomes from societal and healthcare sector perspectives were calculated for adults aged 18-44, 45-64, and ≥65 years; adults with diabetes; and adults with obesity. Seroprotection rates were obtained from the phase3, head-to-head PROTECT trial (NCT03393754). Incidence, vaccine costs, vaccine adherence rates, direct and indirect costs, utilities, transition probabilities, and mortality were obtained from published sources. Health outcomes and costs (2020USD) were discounted 3% annually and reported by vaccine and population. One-way sensitivity and scenario analyses were conducted. RESULTS: In the model, the 3-antigen vaccine led to fewer HBV infections, complications, and deaths compared with the single-antigen vaccine in all modeled populations due to higher rates and faster onset of seroprotection. Compared with the single-antigen vaccine, the 3-antigen vaccine had better health outcomes, more quality-adjusted life-years (QALYs), and lower costs in adults aged 18-64 years, adults with diabetes, and adults with obesity (dominant strategy). For adults aged ≥65 years, the 3-antigen vaccine was cost-effective compared with the single-antigen vaccine ($26,237/QALY gained) below common willingness-to-pay thresholds ($50,000-$100,000/QALY gained). In sensitivity analyses, results were sensitive to vaccine cost per dose, incidence, and age at vaccination. CONCLUSION: The recently approved 3-antigen vaccine is a cost-saving or cost-effective intervention for preventing HBV infection and addressing the long-standing burden of hepatitis B among US adults.

Assessment of immunogenicity and safety across two manufacturing lots of a 3-antigen hepatitis B vaccine, Sci-B-Vac®, compared with Engerix-B® in healthy Asian adults: A phase 3 randomized clinical trial.

BACKGROUND: Sci-B-Vac®, a 3-antigen hepatitis B vaccine (3A-HBV), contains all three recombinant hepatitis B virus (HBV) envelope proteins (S, pre-S1, and pre-S2). In 2005, 3A-HBV manufacturing transferred facilities (A to B), where it continues to be manufactured. METHODS: This phase 3, single-blind, randomized study, conducted at one site in Vietnam, compared efficacy and safety among two 3A-HBV lots, lot A and lot B, and a single-antigen hepatitis B vaccine (1A-HBV), Engerix-B®. Primary objective was to demonstrate equivalence at day 210 of two 3A-HBV lots in seroprotection rate (SPR; defined as percentage of participants achieving hepatitis B surface antigen antibody [anti-HBs] titers ≥ 10 mIU/mL). Secondary objectives were assessing immunogenicity at days 180, 210, and 360, and safety of 3A-HBV. RESULTS: 3A-HBV SPR equivalence was demonstrated at day 210 (lot A: 97.3% [95% CI: 92.4%, 99.4%] vs. lot B: 100.0% [97.0%, 100.0%]). Compared to 1A-HBV, lot B SPR was higher at day 180 (98.3% vs. 81.2%; difference: 17.1% [9.7%, 24.6%]) and non-inferior at day 210 (100% vs. 98.3%; difference: 1.7% [-0.6%, 4.1%]). 3A-HBV lot B showed the same SPR after 2 doses (98.3%) as 1A-HBV after 3 doses (98.3%). Adverse events (AEs) were comparable with both 3A-HBV lots (lot A: 68.7% vs. lot B: 54.2%), but higher than 1A-HBV (35.3%). Vaccination-related AEs included transient injection site pain (38.9%), myalgia (9.3%), and fatigue (7.5%). Eight serious AEs were reported (lot A: 3/134 [2.2%]; lot B: 1/134 [0.8%]; 1A-HBV: 4/133 [2.3%]). One serious AE, syncope, was noted as probably related to study vaccine, lot B. CONCLUSIONS: The two 3A-HBV lots had equivalent immunogenicity, but lot B elicited faster onset of seroprotection and higher anti-HBs titers than both lot A and 1A-HBV in an Asian population. This supports 3A-HBV lot B as an effective choice for HBV vaccination, with a favorable safety profile. ClinicalTrials.gov: NCT04531098.