Direct comparison of two extended-half-life recombinant FVIII products : a randomized, crossover pharmacokinetic study in patients with severe hemophilia A
(2019) In Annals of Hematology 98(9). p.2035-2044- Abstract
BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18–65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0... (More)
BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18–65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUClast, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUClast was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440–3550] IU h/dL versus 2360 [31.8, 2010–2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. ClinicalTrials.gov: NCT03364998.
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- author
- Shah, Anita ; Solms, Alexander ; Wiegmann, Sara ; Ahsman, Maurice ; Berntorp, Erik LU ; Tiede, Andreas ; Iorio, Alfonso ; Mancuso, Maria Elisa ; Zhivkov, Tihomir and Lissitchkov, Toshko
- organization
- publishing date
- 2019-06-24
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Extended half-life, Head-to-head study, Hemophilia A, PEGylated, Pharmacokinetics, Population pharmacokinetics
- in
- Annals of Hematology
- volume
- 98
- issue
- 9
- pages
- 2035 - 2044
- publisher
- Springer
- external identifiers
-
- scopus:85068186510
- pmid:31236667
- ISSN
- 0939-5555
- DOI
- 10.1007/s00277-019-03747-2
- language
- English
- LU publication?
- yes
- id
- ccd3cf09-9348-4f06-b35b-667b452dd99d
- date added to LUP
- 2019-07-10 11:14:43
- date last changed
- 2024-07-11 01:36:14
@article{ccd3cf09-9348-4f06-b35b-667b452dd99d,
abstract = {{<p>BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18–65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUC<sub>last</sub>, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUC<sub>last</sub> was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440–3550] IU h/dL versus 2360 [31.8, 2010–2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. ClinicalTrials.gov: NCT03364998.</p>}},
author = {{Shah, Anita and Solms, Alexander and Wiegmann, Sara and Ahsman, Maurice and Berntorp, Erik and Tiede, Andreas and Iorio, Alfonso and Mancuso, Maria Elisa and Zhivkov, Tihomir and Lissitchkov, Toshko}},
issn = {{0939-5555}},
keywords = {{Extended half-life; Head-to-head study; Hemophilia A; PEGylated; Pharmacokinetics; Population pharmacokinetics}},
language = {{eng}},
month = {{06}},
number = {{9}},
pages = {{2035--2044}},
publisher = {{Springer}},
series = {{Annals of Hematology}},
title = {{Direct comparison of two extended-half-life recombinant FVIII products : a randomized, crossover pharmacokinetic study in patients with severe hemophilia A}},
url = {{http://dx.doi.org/10.1007/s00277-019-03747-2}},
doi = {{10.1007/s00277-019-03747-2}},
volume = {{98}},
year = {{2019}},
}