A. Shah and A. Solms contributed equally to this work.
BAY 81-8973 is a full-length, unmodified, recombinant human factor VIII (FVIII) for the treatment of hemophilia A.
The aim of this study was to compare the pharmacokinetic (PK) profile of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM)
In this phase I, open-label, crossover study, men aged 18–65 years with severe hemophilia A and ≥150 exposure days to FVIII were randomized to receive a single intravenous infusion of 50 IU/kg BAY 81-8973 or rAHF-PFM, followed by crossover to a single infusion of the other treatment. FVIII levels were measured in plasma over 48 h using one-stage and chromogenic assays. PK parameters, including area under the curve from time zero to the last data point (AUClast; primary outcome) and half-life (t ½) were calculated. A population PK model was developed to simulate various treatment scenarios.
Eighteen patients were randomized and analyzed. Using both assays, geometric mean (coefficient of variation [%CV]) AUClast was significantly higher, and t ½ was significantly longer, for BAY 81-8973 versus rAHF-PFM (one-stage, AUClast: 1660 IU·h/dL [29.4] vs. 1310 IU·h/dL [29.0], p < 0.0001; one-stage, t ½: 14.5 [25.7] vs. 11.7 h [27.3], p < 0.0001). Simulations showed that median time to 1 IU/dL was approximately 27% longer for BAY 81-8973 versus rAHF-PFM over doses of 25–50 IU/kg; plasma levels >1 IU/dL could be maintained with 14.4 IU/kg BAY 81-8973 or 39.1 IU/kg rAHF-PFM 3×/week.
BAY 81-8973 showed a superior PK profile versus rAHF-PFM. The same FVIII trough threshold level could be achieved with lower doses of BAY 81-8973 versus rAHF-PFM.
National Hemophilia Foundation. Medical and Scientific Advisory Council (MASAC) recommendations concerning prophylaxis (regular administration of clotting factor concentrate to prevent bleeding). Document #241. 2016. https://www.hemophilia.org/sites/default/files/document/files/241Prophylaxis.pdf. Accessed 25 May 2016.
Lissitchkov T, Tiede A, Valentino L, et al. Pharmacokinetics and efficacy of on-demand treatment with human-cl rhFVIII in previously treated patients with severe hemophilia A [abstract]. Haemophilia. 2012;18(Suppl 3):150.
Kogenate ® FS (antihemophilic factor [recombinant] formulated with sucrose). Full prescribing information. Whippany: Bayer; 2015.
Advate ® (antihemophilic factor [recombinant] plasma/albumin-free method). Full prescribing information. Westlake Village: Baxter Healthcare Corporation; 2014.
- Improved Pharmacokinetics with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method: A Randomized Pharmacokinetic Study in Patients with Severe Hemophilia A
- Springer International Publishing