Indirect Comparison of the Efficacy and Therapy-Related Costs of a Pharmacokinetic and Individualized Prophylaxis Regimen with Simoctocog Alfa Versus Other Extended-Half Life Factor VIII Concentrates

Introduction: Individualized prophylaxis is the gold standard for treating people with hemophilia A. Healthcare costs are high among patients with severe hemophilia A, because of the need for lifelong prophylaxis. Head-to-head comparisons between different therapeutic strategies are generally not feasible in rare diseases such as hemophilia A. Matching-adjusted indirect comparison (MAIC) is a validated statistical methodology, that adjusts study-specific populations based on relevant patient characteristics, to compare reported clinical outcomes from different clinical trials, while minimizing potential biases. Aim and hypothesis: To indirectly compare the efficacy of a pharmacokinetic (PK)-guided individualized prophylaxis regimen with simoctocog alfa (a recombinant FVIII [rFVIII] concentrate produced in human embryonic kidney cells with no chemical modifications or fusion proteins) against five different prophylactic regimens with modified extended half-life (EHL) rFVIIIs. We also estimated and indirectly compared the annual cost differences of each of these regimens. Methods: Individual patient-level data (IPD) were extracted from the NuPreviq clinical trial (simoctocog alfa, N = 65). For comparison, aggregated data was obtained from the following trials with EHL concentrates: pathfinder2 (turoctocog alfa pegol, N = 175), A-LONG (efmoroctocog alfa, N = 117), PROTECT FVIII (damoctocog alfa pegol, N = 110), PROPEL (rurioctocog alfa pegol 1-3% and 8-12%; N = 57 and 58), and XTEND-1 (efanesoctocog alfa, Group A, N = 133). Patients in NuPreviq who did not meet the inclusion criteria for the comparator trial were excluded. To match the aggregate data for each comparator trial, baseline age and body weight were used to re-weight the IPD from NuPreviq. Unanchored indirect comparisons were subsequently performed for the following clinical outcomes: percentage of patients with zero bleeds, annualized bleeding rates (ABRs), and FVIII consumption. The calculated total annual costs were based on the adjusted patient populations from each MAIC and included direct and indirect costs: prophylaxis, on-demand treatment of breakthrough bleeds, non-drug related costs and societal costs. Costs of prophylaxis and on-demand treatment were based on the average selling price in USD according to Medi-span as of July 2024. Results: The percentage of patients with zero bleeds was significantly higher for simoctocog alfa than turoctocog alfa pegol (64% vs 39%: p = 0.001), efmoroctocog alfa (75 vs 45%; p < 0.001), damoctocog alfa pegol (77 vs 38%; p < 0.001), rurioctocog alfa pegol 1-3% (78 vs 42%; p < 0.001) and comparable to rurioctocog alfa pegol 8-12% (77 vs 62%; p = 0.082) and efanesoctocog alfa (64 vs 56%; p = 0.291). The mean total ABR was lower for simoctocog alfa than damoctocog alfa pegol (1.5 vs 4.9; p = 0.001) and comparable to turoctocog alfa pegol (1.7 vs 3.2; p = 0.062), efmoroctocog alfa (1.7 vs 2.9; p = 0.212), rurioctocog alfa pegol 1-3% (1.6 vs 3.6; p = 0.071), rurioctocog alfa pegol 8-12% (1.6 vs 1.6; p = 0.996) and efanesoctocog alfa (1.5 vs 1.1; p = 0.342). The mean weekly prophylactic FVIII use was higher for simoctocog alfa than efmoroctocog alfa (101 vs 85 IU/kg; p < 0.001), damoctocog alfa pegol (97 vs 70 IU/kg; p < 0.001), rurioctocog alfa pegol 1-3% (99 vs 74 IU/kg; p < 0.001), and efanesoctocog alfa (98 vs 52 IU/kg; p < 0.001), but comparable to turoctocog alfa pegol (99 vs 89 IU/kg; p = 0.159), and lower than rurioctocog alfa pegol 8-12% (99 vs 143 IU/kg; p < 0.001). Overall, and regardless of these differences in FVIII weekly use, the annual per-patient estimated cost was lower for simoctocog alfa when compared to the other concentrates: turoctocog alfa pegol ($305,253; 35% cost decrease), efmoroctocog alfa ($287,418, 35% cost decrease), damoctocog alfa pegol ($251,636, 31% cost decrease), rurioctocog alfa pegol 1-3% ($134,218, 20% cost decrease), rurioctocog alfa pegol 8 -12% ($666,280, 55% cost decrease) and efanesoctocog alfa ($513,159, 47% cost decrease). Conclusion: Albeit at a generally higher weekly dose, a PK-guided, individualized prophylaxis regimen with simoctocog alfa offered comparable or significantly improved zero bleed rates and significantly lower or comparable ABRs than prophylactic regimens with EHL rFVIII concentrates. Nevertheless, the estimated annual cost of a simoctocog alfa-based regimen is 20-55% lower than with the other concentrates.