OBJECTIVES: AAV-mediated gene therapy (GT) is a promising new treatment for hemophilia B patients. In contrast with the standard treatments that rely on replacing the missing clotting factor, either on-demand (OD) or by regular prophylactic infusions (Pro), GT provides endogenous factor production long-term after a single infusion. Patients who have factor inhibitors or neutralizing AAV-antibodies are mostly not eligible to receive GT and are thus often excluded from cost-effectiveness analyses. Our study examined the cost-effectiveness of GT compared to alternative treatments in two target populations, the GT-eligible cohort versus the total hemophilia B population.

METHODS: Six treatment approaches were compared: three different strategies - OD, Pro, and GT - first two were administered with either standard (SHL) or extended half-life (EHL) factor replacement. For GT, each factor replacement regimen was used before GT infusion and after the GT effect waned. A cost-effectiveness threshold of $150,000 was adopted and GT–SHL was used as reference approach for comparison. The population-based analysis was conducted using two cohorts: a GT-eligible cohort and all patients, inclusive of GT ineligible patients.

RESULTS: For OD–SHL, OD–EHL, Pro–SHL, Pro–EHL, GT–SHL and GT–EHL, the GT-eligible group costs|QALYs were as follows, $8,110,000|13.80, $7,440,000|14.26, $10,060,000|23.35, $16,690,000|24.14, $6,390,000|24.38 and $9,730,000|24.94, respectively. Accordingly, GT–SHL (the reference approach) dominated the first four alternatives. Results for the entire population were $8,200,000|13.8, $7,690,000|14.26, $11,190,000|23.07, $18,500,000|23.56, $8,580,000|23.81 and $14,020,000|24.04, respectively. Accordingly, GT–SHL was more costly but cost-effective compared to the first two alternatives with an incremental cost-effectiveness ratio (ICER) of $40,000/QALY and $90,000/QALY, and dominant compared to the third and fourth.

CONCLUSIONS: By taking a population-based approach and including both eligible and ineligible GT patients, we identified additional aspects for policy makers to consider. There is added value in exploring the impact of different inclusion and exclusion criteria when choosing the target population in a cost-effectiveness analysis.