Comparative Pharmacokinetics of Two Recombinant FVIII Concentrates in Chinese Pediatric Patients with Severe Hemophilia A: A Single-Center Study

K. Huang, R. Wu, Z. Chen, Y. Zhen, X. Wu, G. Li

Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China

Abstract Number: PB0319

Meeting: ISTH 2020 Congress

Theme: Coagulation and Natural Anticoagulants » FVIII/IX

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 t_1/2 (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 t_1/2 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.

[Individual comparison between Kogenate FS and Kovaltry of the (A) trough FVIII level in daily prophy]

	Kogenate FS	Kovaltry	statistic	P value
T1/2(h)	11.51±2.93	13.76±3.14	5.993	<0.001
CL (ml/kg/h)	3.79±1.47	3.35±1.12	1.178#	0.260
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
MRT(h)	11.18(10.53,15.77)	18.22(15.0,20.22)	-3.296*	0.001
Vss (dL/kg)	0.48(0.38,0.53)	0.53(0.50,0.59)	-2.691*	0.007
IVR (kg/dL)	2.00(1.62,2.28)	1.72(1.65,1.89)	-1.695*	0.090

[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 January 28, 2022.

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