Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates

Kun Huang; Yingzi Zhen; Gang Li; Xinyi Wu; Zhenping Chen; Runhui Wu

doi:10.1002/rth2.12686

Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates

Res Pract Thromb Haemost. 2022 Mar 25;6(2):e12686. doi: 10.1002/rth2.12686. eCollection 2022 Feb.

Authors

Kun Huang¹, Yingzi Zhen¹, Gang Li², Xinyi Wu¹, Zhenping Chen², Runhui Wu¹

Affiliations

¹ Hematology Center National Center for Children's Health Beijing Children's Hospital Capital Medical University Beijing China.
² Hematologic Disease Laboratory Beijing Pediatric Research Institute National Center for Children's Health Beijing Children's Hospital Capital Medical University Beijing China.

Abstract

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

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

Methods: Forty-seven boys with severe hemophilia A 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 participant with a five-point assay during the study period from 6 months before switching to 6 months after switching. FVIII levels were detected by one-stage assay, and PK profiles were calculated by noncompartmental assay. Annualized bleeding rates were collected through participant' bleed logs.

Results: Longer half-life time (Kogenate FS group: 14.4 vs 11.9 hours, P < .0001; Advate group: 13.4 vs 9.7 hours, P < .0001; GreenMono group: 15.1 vs 10.7 hours, P < .001]) and lower clearance (Kogenate FS group: 3.3 vs 3.9 mL/kg/h, P < .01; Advate group: 3.7 vs 5.9 mL/kg/h, P < .01; GreenMono group: 3.0 vs 5.1 mL/kg/h, P < .01) were observed with Kovaltry. In addition, longer mean residential time (P < .01) and higher area under the curve (P < .01) were demonstrated. No statistical difference was found in in vivo recovery between Kovaltry and the other FVIII products. Participants who switched to Kovaltry from three other FVIII concentrates with the same dosing regimens obtained higher trough FVIII levels and better protection with reduced annualized bleeding rates.

Conclusion: Compared with Kogenate FS, Advate, and GreenMono, Kovaltry showed enhanced PK profiles, which contributed to reduced bleeding rates.

Keywords: bleeding; child; factor VIII; hemophilia; pharmacokinetics.