Pharmacokinetic Comparison of Two EHL Products in Hemophilia A

WAPPS-HEMO Application and Population PK Profile Determination

For patients with hemophilia A, determining an individual pharmacokinetic (PK) profile helps set an optimal prophylactic regimen for administering factor VIII coagulation concentrates. This is already being implemented in many hemophilia centers, and the WAPPS-HEMO program (Web-Accessible Population Pharmacokinetic Service − Hemophilia), based on Bayesian analysis, has become very valuable for analyzing individual PK profiles. The population method allows determining the PK profile even when examining a limited number of samples.

Study Methodology and Course

The authors of the cited work used the WAPPS-HEMO application to evaluate several variables obtained from pharmacokinetic (PK) studies conducted at one center, specifically for 2 recombinant FVIII products with extended half-lives – rFVIIIFc and pegylated FVIII (PEG FVIII; Adynovi). Data were obtained from the same patients for both products due to a nationwide switch of these products.

The study was conducted between August 2016 and June 2017, evaluating PK variables obtained from 23 moderate and severe hemophilia patients before and after the therapy switch. Retrospective analysis was done on the data collected during treatment with rFVIIIFc and the data obtained after the necessary switch to PEG FVIII.

Results

Only minimal differences in PK were observed between rFVIIIFc and PEG FVIII, but some were statistically significant. These included in vivo recovery (average 2.73 IU/dl per IU/kg vs. 2.41 IU/dl per IU/kg), clearance (average 0.163 ml/h vs. 0.194 ml/h), and the distribution volume in the steady state (average 42.5 ml/kg vs. 49.8 ml/kg). There was also a smaller, non-significant trend of higher values for PEG FVIII in terminal half-life, area under the curve, and the predicted time to 5% and 1% residual FVIII after infusion.

Conclusion

The population PK analysis showed slight differences between the two extended half-life FVIII products, with significant differences observed in the parameters in vivo recovery, clearance, and distribution volume. The switch between the two studied products did not adversely affect patient care. Additionally, the benefit of population PK analyses for routine practice was confirmed.

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Source: Teitel J., Sholzberg M., Iorio A. Extended half-life factor VIII concentrates in adults with hemophilia A: comparative pharmacokinetics in two products. Res Pract Thromb Haemost 2021 Feb 23; 5 (2): 349−355, doi: 10.1002/rth2.12476.