PB1252 - Value of Hemophilia Drug Treatment Using Analysis of the Area Under the Curve

Background: Standard of care for hemophilia A is prophylaxis with standard half-life (SHL) or extended half-life (EHL) recombinant factor VIII (rFVIII) replacement therapy (Berntorp, 2016). Area under the plasma level curve (AUC) quantifies FVIII levels over time after infusion and has been proposed as an outcome-oriented way to assess comparative product value using indirect comparisons in a decision-analytic model (Persson, 2022).

Aims: To update the analyses with a more complete comparison, including most FVIII products and additional data (Solms, EAHAD 2022).

Methods: Pharmacokinetic (PK) data from 9 clinical cross-over studies were indirectly compared as described previously. In the new scenario, octocog alfa (Advate) was set as the common comparator. The comparators included 3 EHL and 5 SHL products (Table 1). Data were extracted from the studies as the mean FVIII level in the blood at each sampling point, and AUC was calculated for all products using a loglinear continuous function. Results are presented at 5 ranges of predefined minimum and maximum levels of FVIII (0–40 IU/dL). Sensitivity analyses were performed based on assay type and dose-adjustment to 50 IU/kg.

Results: Estimated AUCs for all products compared with octocog alfa (Advate) in base-case analysis are shown in Figure 1 and Table 1. Damoctocog alfa pegol (Jivi) and efmoroctocog alfa (Elocta) had the largest AUCs compared with Advate (+71%–90% and +66%–73%, respectively) depending on min/max range. Among all SHLs, lonoctocog alfa (Afstyla) had a larger AUC compared with Advate (+18%–27%). After assay type and dose-adjustment sensitivity analyses, all EHLs still had larger AUCs compared to Advate.

Conclusion(s): Results from this updated analysis continue to show larger AUCs for EHLs compared with all SHLs, with damoctocog alfa pegol having the largest AUC. These results suggest that EHLs may offer longer infusion intervals due to greater FVIII levels over time.

Funded by Bayer.