VPB0692 - Enhanced pharmacokinetics and improved clinical outcomes in young hemophiliac boys after the switch to BAY 81-8973 from other standard half-life FVIII concentrates

Background: BAY81-8973(Kovaltry,Bayer,US) was reported with enhanced pharmacokinetic(PK) profiles compared with some other standard half-life(SHL) FVIII concentrates. Limited head-to-head comparative studies were conducted in a real-world setting.

Aims: To make head-to-head comparisons of PK and clinical outcomes between Kovaltry and the other three SHL FVIII concentrates.

Methods: Forty-seven hemophiliac boys were enrolled and divided into three groups according to their previously used FVIII concentrates (Kogenate FS, N=22; Advate, N=14; GreenMono, N=11). Two separate PK tests were conducted in each patient with a five-point assay during the study period from 6 months pre-switch to 6 months post-switch. FVIII levels were detected by one-stage assay and PK profiles were calculated by Non-Compartment Assay. Annualized bleeding rates were collected through patients’ bleeds logs during the one-year study period.

Results: Longer half-life time (t1/2)[Kogenate FS group:14.36±1.92 vs. 11.92±2.41h,P < 0.0001); Advate group(13.41±1.44 vs. 9.67±1.74h,P < 0.0001); GreenMono group(15.07±3.36 vs. 10.70±1.66h,P < 0.001)] and lower clearance[Kogenate FS group:3.26±1.06 vs. 3.92±1.16ml/kg/h, P< 0.01; Advate group:3.70±1.20 vs. 5.91±2.22ml/kg/h,P < 0.01; GreenMono group, 3.02±1.24 vs. 5.07±1.55ml/kg/h,P < 0.01] were observed in Kovaltry as well as longer mean residential time(P < 0.01) and higher area under curve(P < 0.01). No statistical difference was found in in-vivo recovery between Kovaltry and other FVIII products. Patients with higher VWF:Ag levels or blood group non-O had a longer augment of t1/2 during the switch in all three groups. Significantly reduced annualized bleeding rates(ABR) were observed in all three groups(P < 0.05) as well as improved annualized joint bleeding rates(AJBR) and annualized spontaneous bleeding rates(ASBR) in the Advate group and GreenMono group. Despite the P-values did not reach a statistical difference in the Kogenate FS group, the decreased mean value of AJBR(1.55 vs. 2.18) and ASBR(0.86 vs. 1.54) indicated the improvements.

Conclusion(s): Compared with Kogenate FS, Advate, and GreenMono, Kovaltry have enhanced PK profiles, which contributed to later-observed reduced bleeding rates.