Abstract Number: PB0319
Meeting: ISTH 2020 Congress
Background: Recently, the treatment of patients with severe hemophilia A(SHA) in China has been required to switch from Kogenate FS to Kovaltry. However, no head-to-head comparison of these two recombinant FVIII pharmacokinetics (PK) concentrates were reported on the same pediatric patients.
Aims: To compare the PK profiles of Kogenate FS with Kovaltry on the same pediatric patient with severe hemophilia A.
Methods: This study enrolled 14 Chinese pediatric SHA patients (male, mean age 5.67 years, range 2.83-9.42y; 9 O blood type), who switched from Kogenate FS to Kovaltry for prophylaxis. PK study was performed on these two FVIII products for each patient separately. After a 3-day washout period, each patient received a single infusion of 50IU/Kg. Blood samples were collected at pre-dose, 1h, 9h, 24h and 48h post-infusion for pharmacokinetic assessment. FVIII activity was determined by one-stage assay and the PK parameters were calculated by WinNonlin software. Annual bleeding rate(ABR) and annual joint bleeding rate(AJBR) were collected by patients’ daily record.
Results: Mean time between two PK tests were 9.64 months. Compared with Kogenate, Kovaltry had a longer t1/2 (13.76 vs. 11.51 hours, P< 0.001), higher AUC (1745 vs. 1609 IU h/dL, P< 0.05)/AUClast (1658 vs. 1478 IU h/dL,
P< 0.05), longer MRT (18.22 vs. 11.18 hours, P=0.001) and higher Vss (0.53 vs. 0.48 dL/kg, P< 0.01). No statistical difference was observed in CL and IVR. Patients with higher VWF:Ag level/blood type non-O had a longer augment of t1/2 after the switch. The median trough FVIII level raised from 1 to 2.25 IU/dL. The ABR and AJBR decreased from 3.89 and 3.58 using Kogenate FS to 2.0 and 0.72 using Kovaltry.
Conclusions: Kovaltry showed better PK profiles and clinical outcomes comparing with Kogenate FS. Patients with higher VWF:Ag level or blood type non-O benefit more from the switch.
|Kogenate FS||Kovaltry||statistic||P value|
|AUC (IU h/dL)||1609(1065,1739)||1745(1359,1952)||-2.411*||0.016|
|AUClast (IU h/dL)||1478(1046,1663)||1658(1299,1804)||-2.271*||0.023|
[PK parameters of Kogenate FS and Kovaltry]
To cite this abstract in AMA style:Huang K, Wu R, Chen Z, Zhen Y, Wu X, Li G. Comparative Pharmacokinetics of Two Recombinant FVIII Concentrates in Chinese Pediatric Patients with Severe Hemophilia A: A Single-Center Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/comparative-pharmacokinetics-of-two-recombinant-fviii-concentrates-in-chinese-pediatric-patients-with-severe-hemophilia-a-a-single-center-study/. Accessed September 22, 2023.
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