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

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.

Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A

“…Data on inhibitor development related to factor switching in children are still scarce. In a recent publication, Huang et al reported that none of 47 boys aged less than 18 years switched to one of three standard half-life factors (Kovaltry, Advate, and GreeMono) developed inhibitor (14). Similar results were published by Escuriola-Ettinghausen et al however, only 14 out of 68 patients switched to turoctokog-alpha were younger than 12 years (15).…”

“A personalized limited sampling approach to better estimate terminal half‐life of FVIII concentrates”: Comment from Huang et al.

“…Another comparative PK study with rigorous head-to-head design also found that a patient could have his or her FVIII half-life time change up to 41% (from GreenMono to Kovaltry: 10.7 ± 1.7 h to 15.1 ± 3.4 h). 8 Thus, we suggest the authors explore more FVIII concentrates, especially for those that have been reported with shorter or longer half-life times.…”

“…In my experience with more than 300 PK tests in pediatric patients with hemophilia, it would not be hard to control the dose within 40-60 IU/kg for the PK infusion despite different vial sizes. [6][7][8]10 But considering the wide use of WAPPS-Hemo, the dose could vary among different hemophilia centers. To facilitate clinical application, the authors might consider reporting corresponding suggested personalized sampling times by different common dose ranges.…”

Letter to the Editor Regarding “Cost-Effectiveness Analysis of Pharmacokinetic-Guided Prophylaxis Versus Standard Prophylaxis in Adults with Severe Hemophilia A in China”

“…Thus, the authors could also seek PK parameters of different FVIII concentrates in published clinical trials as they are conducted in the Chinese population. Actually, the variability of PK parameters among different FVIII concentrates was also reported, which could be a potential bias for this study and there could have been better relevant descriptions in the limitations section [ 12 , 13 ].…”