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

Pouplard, Claire; Sattler, Laurent; Ryman, Anne; Eschwège, Valérie; Maistre, Emmanuel de; Flaujac, Claire; Szymezak, Jean; Grand, François Le; Repessé, Yohann; Galinat, Hubert; Donnard, Magali; Ternisien, Catherine; Iorio, Alfonso; Chelle, Pierre; Jeanpierre, Emmanuelle

doi:10.1111/hae.13946

Cited by 10 publications

(12 citation statements)

References 21 publications

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“…Recombinant extended half‐life (EHL) FVIII concentrates were developed with the goal of reducing infusion frequency and improving treatment outcomes by securing higher trough levels. The half‐lives of EHL FVIII products are approximately 1.5 times longer compared to standard half‐life (SHL) concentrates 9–12 . Extensive clinical trials have demonstrated the safety and efficacy of EHL FVIII products 13 .…”

Section: Introductionmentioning

confidence: 99%

“…The half-lives of EHL FVIII products are approximately 1.5 times longer compared to standard half-life (SHL) concentrates. [9][10][11][12] Extensive clinical trials have demonstrated the safety and efficacy of EHL FVIII products. 13 However, it is not straightforward how the improved pharmacokinetics (PK) are taken advantage of in clinical practice when dosing and determining infusion frequency.…”

Section: Introductionmentioning

confidence: 99%

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Switching from standard to extended half‐life FVIII prophylaxis in haemophilia A: Comparison of factor product use, bleed rates and pharmacokinetics

et al. 2022

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Introduction Majority of haemophilia A patients in our comprehensive care centre have switched from standard half‐life (SHL) to extended half‐life (EHL) FVIII products in a short time. Aim We compared the clinical and laboratory outcomes between SHL and EHL FVIII prophylaxis in product switchers. Methods This is a retrospective inception cohort of all adult haemophilia A patients switched to EHL (rFVIIIFc or rFVIII‐PEG) prophylaxis in our centre. Dosing, product utilization, annualized bleed rates (ABR), treatment regimen and pharmacokinetics by Web Accessible Population Pharmacokinetic Service (WAPPS)‐Hemo were compared between SHL and EHL. Results We included 38 patients, whose median age was 38 years (range 17–75). Median FVIII dose was 23 IU/kg for SHL versus 25 IU/kg for EHL. After switching, weekly infusions decreased by 29% from median 2.8 (every 2.5 days) to 2.0 (every 3.5 days) (P = <.001) and factor consumption for prophylaxis by 17% from 60 to 50 IU/kg/week (P = <.001). Weekly infusions decreased in 71% and FVIII utilization in 55% of patients. ABR remained low (1.0 for SHL and .5 for EHL, respectively). In pharmacokinetics, the half‐life of FVIII increased from median 13 to 21 h after switching. Times above .01 and .03 IU/ml improved from 85 to 131 h and from 65 to 106 h. Half‐lives of the SHL products and von Willebrand factor levels predicted half‐lives with the EHL products. Conclusions Our cohort study confirms the successful experience of switching to EHL FVIII products, with decreased infusion frequency, factor consumption and excellent clinical efficacy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Switching from standard to extended half‐life FVIII prophylaxis in haemophilia A: Comparison of factor product use, bleed rates and pharmacokinetics

et al. 2022

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“…The pharmacokinetics of this EHL rFVIII product are age-dependent, with clearance decreasing and, therefore, the terminal elimination half-life (t½) increasing, with increasing age [2] (Table 1). The t½ of efmoroctocog alfa is ≈ 1.4−1.8 times longer than that of conventional FVIII/rFVIII preparations as a result of the Fc portion binding to the neonatal Fc receptor, which is part of a naturally occurring pathway that protects immunoglobulins (and Fc fusion proteins) from lysosomal degradation by recycling them back into the circulation [2,5,10].…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

Efmoroctocog Alfa: A Review in Haemophilia A

Frampton

2021

Drugs

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Efmoroctocog alfa (Elocta ® , Eloctate ® , Eloctate™), an extended half-life (EHL) recombinant factor VIII (rFVIII)-Fc fusion protein, is approved for the treatment and prophylaxis of bleeding in patients with haemophilia A. The efficacy of efmoroctocog alfa in the prevention and treatment of bleeding in previously treated patients (PTPs) and previously untreated patients (PUPs) with severe haemophilia A has been demonstrated in phase III studies; this includes its use in the perioperative setting (in PTPs). Furthermore, the effectiveness of efmoroctocog alfa in clinical practice has been confirmed in numerous real-world studies; compared with conventional, standard half-life (SHL) FVIII products, prophylaxis with this EHL FVIII product achieved similar or reduced bleeding rates with fewer injections. Efmoroctocog alfa was generally well tolerated; inhibitors occurred in approximately one-third of PUPs in a phase III study. Efmoroctocog alfa is an established and effective EHL FVIII replacement therapy for the management of haemophilia A. Compared with SHL FVIII products, EHL FVIII products such as efmoroctocog alfa have the potential to optimise prophylactic outcomes by decreasing the burden of treatment or increasing the level of bleed protection. Plain Language SummaryCoagulation factor VIII (FVIII) replacement therapy is the mainstay of haemophilia A treatment; FVIII prophylaxis is the standard of care for severe disease. EHL rFVIII products have been developed to decrease the burden and/or increase the effectiveness of prophylaxis compared with conventional FVIII/rFVIII products which, due to their shorter half-lives, require more frequent injections. Efmoroctocog alfa (Elocta ® , Eloctate ® , Eloctate™), a first-in-class rFVIII-Fc fusion protein with a half-life ≈ 1.4−1.8 times longer than that of conventional FVIII/rFVIII preparations, is approved for the prophylaxis and treatment of bleeding in patients with haemophilia A in various countries worldwide. The efficacy of efmoroctocog alfa has been demonstrated in phase III trials in patients with severe haemophilia A, and its effectiveness, particularly as FVIII prophylaxis, has been confirmed in numerous studies in clinical practice. The rate of formation of neutralizing anti-FVIII antibodies (inhibitors) with efmoroctocog alfa is similar to that with other FVIII/rFVIII products. Based on a large body of clinical trial and real-world data, efmoroctocog alfa is an established and effective EHL FVIII replacement therapy for the management of haemophilia A.

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“…While randomized clinical trials remain the gold standard to establish efficacy and safety of new therapeutic agents, data from clinical routine produce evidence of therapeutic effectiveness in real-world practice settings. Extensive analyses from clinical trials have been published (13)(14)(15)(16)(17)(25)(26)(27)(28)(29)(30)(31), but uncertainties prevail among physicians despite of a recent uptake in published real-world evidence (32)(33)(34)(35)(36)(37)(38). Especially, the inhibitor risk of patients with a prior history of inhibitors is an issue of debate since those patients are excluded from clinical trials.…”

Section: Figurementioning

confidence: 99%

Real-world clinical experience of extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) in comparison to conventional factor products in patients with severe hemophilia A

Oldenburg¹,

Goldmann²,

Marquardt³

et al. 2021

J Current Med Res Opinion

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Introduction: The recombinant factor FVIII Fc fusion protein (rFVIIIFc) is a first-in-class extended half-life FVIII product to treat patients with hemophilia A. The safety, efficacy and prolonged half-life of rFVIIIFc was demonstrated in the phase 3 studies A-LONG, Kids A-LONG and the extension study ASPIRE. Despite robust efficacy and safety data of rFVIIIFc therapy from clinical trials, evidence on the effectiveness of rFVIIIFc use in real-world remains scarce. Our analysis aimed at investigating the effectiveness of prophylactic rFVIIIFc treatment in routine clinical use in Germany. Material and Methods: Twenty-seven patients with severe hemophilia A, who switched from prophylaxis with conventional recombinant factor VIII (rFVIII) products to rFVIIIFc, were included. Annualized bleeding rates, factor consumption, number of injections and adherence to prophylaxis were compared. The retrospective period prior switching to rFVIIIFc was three years, while the mean follow-up period after switching to rFVIIIFc was 24.9 months. Results: Switching to rFVIIIFc led to a 33.7% reduction in mean annualized number of injections and a 18.3% reduction in mean annualized factor consumption while maintaining low bleeding rates. The mean annualized bleeding rate (ABR) was 2.5 and 1.7 for rFVIII and rFVIIIFc, respectively. The adherence improved from 87% to 94%. During the follow-up period eleven surgeries were performed; all with a hemostatic response rated as excellent. No FVIII inhibitor formation after switching to rFVIIIFc has been detected. Conclusion: Real-world treatment with rFVIIIFc was associated with substantial reductions in consumption and injection frequenies while maintaining low bleeding rates supporting safety and efficacy data from clinical trials.

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

Cited by 10 publications

References 21 publications

Switching from standard to extended half‐life FVIII prophylaxis in haemophilia A: Comparison of factor product use, bleed rates and pharmacokinetics

Switching from standard to extended half‐life FVIII prophylaxis in haemophilia A: Comparison of factor product use, bleed rates and pharmacokinetics

Efmoroctocog Alfa: A Review in Haemophilia A

Real-world clinical experience of extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) in comparison to conventional factor products in patients with severe hemophilia A

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