Abstract Number: PB0559
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Previously conducted head-to head (H2H) studies based on an intra-individual cross-over design in patients with severe hemophilia A, compared the pharmacokinetic (PK) parameters between BAY 94-9027 and three other recombinant factor VIII (rFVIII) products. In all studies, BAY 94-9027 showed improved PK versus the comparator.
Aims: To use population PK (popPK) modeling of available H2H PK data to predict weekly FVIII consumption of different regimens of BAY 94-9027 (Jivi), compared with antihemophilic factor (recombinant) formulated with sucrose (Kogenate-FS), rFVIIIFc (Elocta) and BAX 855 (Adynovi).
Methods: Three H2H studies compared PK of BAY 94-9027 with antihemophilic factor (recombinant) FS, rFVIIIFc or BAX 855. For each study, the respective individual PK parameters from popPK modeling were used to predict steady-state FVIII trough (pre-dose) levels for each product for different prophylaxis regimens. Using these predicted trough levels, the individual dose required to maintain the patients consistently above threshold level of clinical interest, such as 3 IU/dL, was determined. The respective predicted weekly FVIII (IU/kg) consumption was calculated depending on the regimen, and the ratio of the predicted weekly dose for BAY 94-9027 versus the comparator was estimated.
Results: Overall, 49 patients were included in this analysis (n=14, antihemophilic factor [recombinant] FS; n=17, rFVIIIFc; n=18, BAX 855). Targeting a threshold of 3 IU/dL in patients on a prophylaxis regimen of twice a week required lower median doses by approximately 58%, 33% and 35% for treatment with BAY 94-9027 compared to treatment with antihemophilic factor (recombinant) FS, rFVIIIFc and BAX 855 respectively (Table 1). Other target thresholds and regimens will be presented.
| Product | n | Weekly consumption, IU/kg, median | Ratio, median | Reduction with Jivi, % |
|---|---|---|---|---|
| BAY 94-9027 | 14 | 64.6 | 0.416 | 58 |
| Antihemophilic factor (recombinant) FS | 14 | 175 | ||
| BAY 94-9027 | 17 | 96.6 | 0.666 | 33 |
| rFVIIIFc | 17 | 166 | ||
| BAY 94-9027 | 18 | 79.2 | 0.647 | 35 |
| BAX 855 | 18 | 138 |
Table 1 Predicted FVIII consumption of PK tailored treatment with BAY 94-9027 compared with standard- and extended-half-life rFVIII products targeting a FVIII trough level of 3 IU/dL on a prophylaxis regimen of twice a week
Conclusions: These dose predictions reveal the potential of BAY 94-9027 in reducing FVIII consumption compared with other rFVIII products, while maintaining the same FVIII trough level, and thereby similarly efficient protection from bleeds.
To cite this abstract in AMA style:
Solms A, Shah A, Berntorp E, Tiede A, Iorio A, Bröker A, Mancuso ME. Predicted FVIII Consumption of BAY 94-9027 Compared with Standard- and Extended-half-Life FVIII Products in Patients with Severe Hemophilia A [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/predicted-fviii-consumption-of-bay-94-9027-compared-with-standard-and-extended-half-life-fviii-products-in-patients-with-severe-hemophilia-a/. Accessed September 21, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/predicted-fviii-consumption-of-bay-94-9027-compared-with-standard-and-extended-half-life-fviii-products-in-patients-with-severe-hemophilia-a/