Comparative pharmacokinetics of two extended half‐life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: Is there a difference?

Abstract

Background:A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate.Objectives: Compare the PK profiles of Eloctate vs Adynovate in the same boys.Methods: Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)-Hemo PK tool. Results: Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9;

Multicentre pharmacokinetic evaluation of rFVIII‐Fc (efmoroctocog alfa) in a real life and comparison with non‐extended half‐life FVIII concentrates

“…With this population PK method analysis, the FVIII half‐lives measured were similar to those previously evaluated, and our data confirmed the longer half‐life of efmoroctocog alfa (12.9 hours) compared to those of non‐EHL FVIII (9.2 hours). The elimination half‐life of rFVIII‐Fc measured by Carcao et al using the same PK tool (WAPPS‐Hemo) in 25 adolescents was longer (16.1 hours), and this difference was possibly due in part to the low number of samples collected 72 hours postinfusion (9%) in our patients. However, the elimination half‐life ratio of 1.4 that we measured was similar to that reported by Mahlangu, and highly variable from one patient to another in accordance with another study, with ratio values ranging from 0.79 to 2.98 in treated children .…”

“…But this difference was negligible when FVIII levels were below 0.2 IU/mL, in accordance with recent data. 7 Usually, FVIII lev- mL, and IVR assessed with OSA was always lower than that measured by CSA. In our study, the incremental recovery of FVIII was 2.2 (range 1.3-4.4) with OSA and identical to that reported in the Phase 3 study of rFVIII-Fc.…”

“…Our study is the first to present real‐life pharmacokinetics parameters obtained with rFVIII‐Fc in more than 100 severe haemophilia A patients followed by 13 French centres. Only one other article recently reported population PK data collected in 25 haemophilia A adolescents who had to switch from Eloctate ® to Adynovate ® …”

“…To date, two pivotal studies (A‐Long Study and Kids A‐long) reported a mean half‐life ratio of 1.5 when rFVIII‐Fc was compared with Advate ® . Since then, only one real‐life study has reported PK profiles of efmoroctocog alfa infused in 25 adolescents with haemophilia A …”

“…Since then, only one real-life study has reported PK profiles of efmoroctocog alfa infused in 25 adolescents with haemophilia A. 7 To further evaluate the benefit in terms of PK of this long-acting FVIII compared to conventional non-EHL FVIII, the Biology Study Group on Haemorrhagic Diseases (BIMHO) conducted a retrospective multicentre study to collect half-life analyses performed with efmoroctocog alfa in real life in treated haemophilia A patients and previously with a standard half-life (SHL) FVIII in some cases. Since several French centres had analysed their data in the Wapps-Hemo network, we also compared our results obtained using a non-compartmental model with those generated by a population PK model.…”