1. Potential Cost-Effectiveness of a Tuberculosis Vaccine: Implications for Clinical Trials Jared Ditkowsky Kevin Schwartzman MD, MPH Montreal Chest Institute, McGill University Supported by: Montreal Chest Institute Research Centre *No conflicts to disclose

2. Aims To compare cost, projected TB cases, and projected TB mortality, between current practice (neonatal BCG) and the addition of an MVA85A booster, in a cohort of South African infants using a 10-year time frame, and a societal perspective. To examine different scenarios for vaccine efficacy and attendant clinical trial size and costs. Bacille Calmette-Guérin (BCG) vaccine is currently the only licensed tuberculosis vaccine Previous modeling has highlighted the potential role of novel vaccines in TB control The new MVA85A vaccine (Oxford-Emergent) has completed accrual in a Phase IIb clinical trial in South African infants Background

3. Methods Decision analysis model with multiple Markov processes calibrated to simulate characteristics of the South African population (TreeAge Pro®) Cohort of 960,763 infants entering the population, with outcomes projected over the following 10 years TB annual risk of infection 4.12%, HIV prevalence at birth 5.45% Vaccines assumed to prevent primary progression to active TB disease; protective efficacy 50% for BCG alone Research and development costs (prorated to South Africa’s potential global market share) were incorporated into the cost per infant Research and development reflected different sample size requirements for phase 3 studies, according to varying efficacy values for the combination of neonatal BCG + MVA85A booster.

4. Predicted Outcomes with Varying Efficacy Values for BCG + MVA85A Booster * Costs expressed in millions USD (2009) Protective Efficacy 85%80%75%70% Total Cost BCG*$84.1 Costs Saved with MVA85A* $14.96$12.66$10.26$7.89 Active TB Cases with BCG 16,190 Cases Averted with MVA85A 2,6972,3121,9271,542 TB Deaths with BCG 5,130 Deaths Averted with MVA85A 809693576459

5. * Length of follow-up 2 years; assumed active TB risk = 3% in control arm †All costs expressed in millions USD (2009) ‡Current Phase IIb clinical trial is designed to detect a 60% increase in efficacy over BCG alone, with 90% power Sample Size and Trial Costs for Varying MVA85A Efficacy Values MVA85A + BCG Combined Efficacy; Clinical Trial Power Phase III Sample Size*Total Cost† 85%; Power 90%N/A‡$90 80%; Power 90%N/A‡$90 75%; Power 90%4,367$213.12 Power 80%3,328$197.6 70%; Power 90%7,162$321.5 Power 80%5,433$265.6

6. Sensitivity Analysis Varied ParameterTB Cases Prevented by Adding MVA85A TB Deaths Prevented Cost Savings ($ millions) Base Case (80% efficacy)2,312692$12.66 TB ARI (Low End, 2.5%)1,460432$7.46 TB ARI (High End, 8.14%)4,1601,259$23.91 HIV Prevalence at Birth, Halved to 2.73% 2,200682$12.61 HIV Prevalence at Birth, Doubled to 10.9% 2,430720$12.69 Favorable Scenario5,3933199$33.94 Unfavorable Scenario765224$1.1 Favorable Scenario I.Halved: MVA85A Cost per Dose Probability of TB Diagnosis II.Doubled: Probability of Drug-Resistant TB Probability of Acquiring HIV Cost per DOT Visit III.BCG + MVA85A Efficacy = 85% Unfavorable Scenario I Halved: Probability of Drug-Resistant TB Probability of Acquiring HIV Cost per DOT Visit II Doubled: MVA85A Cost per Dose III Probability of TB Diagnosis = 90% IV BCG + MVA85A Efficacy = 70%

7. Discussion The BCG + MVA85A booster strategy appears cheaper than BCG alone, and to reduce TB morbidity and mortality for all combined efficacy values of ≥ 70% ▫Even when prorated clinical trial costs are built into vaccination program costs With the “unfavorable” scenario, there were still associated cost savings as well as health gains This analysis underestimates health gains and cost savings, to the extent that it focuses on a single birth cohort