The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.
“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the.
In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.
The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.
After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.
In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)
“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.
With respect to safety, no adverse events were reported among study participants.
The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.
“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.
The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.
SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. .