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.
[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 September 22, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/comparative-pharmacokinetics-of-two-recombinant-fviii-concentrates-in-chinese-pediatric-patients-with-severe-hemophilia-a-a-single-center-study/