Extended half‐life factor VIII concentrates in adults with hemophilia A: Comparative pharmacokinetics of two products

Teitel, Jerome; Sholzberg, Michelle; Iorio, Alfonso

doi:10.1002/rth2.12476

Cited by 6 publications

(8 citation statements)

References 23 publications

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“… 15 Another Canadian study reported a retrospective analysis of pharmacokinetic data from 23 patients with hemophilia A who were switched from efmoroctocog alfa to rurioctocog alfa pegol. 16 The results showed minor differences in the pharmacokinetic profile of the two agents, which were statistically significant (p<0.05 for all) for in vivo recovery (mean 2.73 vs 2.41 IU/dL per IU/kg), clearance (mean 0.163 vs 0.194 mL/h), and volume of distribution at steady state (mean 42.5 vs 49.8 mL/kg), respectively. The authors commented, however, that the clinical implications of these differences are uncertain.…”

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

“…The authors commented, however, that the clinical implications of these differences are uncertain. 16 Indeed, an earlier study from the same centers showed that the pharmacokinetic profiles of efmoroctocog alfa to rurioctocog alfa pegol in adolescents with hemophilia A were almost identical (mean [range] terminal half-life 16.1 (10.4-23.4) hours vs 16.7 (11.0-23.6) hours, respectively [p=NS]). 17 There is a need for further real-world evidence on EHL products to improve the understanding of prophylaxis dosing patterns associated with each EHL rFVIII to inform health care decision-making and identify the most appropriate treatment regimens for different patient groups.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States

Wu¹,

Sun²,

Fan³

2022

JBM

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Background US patients with hemophilia A can receive prophylaxis with extended half-life recombinant factor VIII (rFVIII) products, including efmoroctocog alfa (fragment crystallizable fusion protein) and rurioctocog alfa pegol (antihemophilic factor [recombinant], PEGylated). Objective To evaluate dosing patterns and weekly consumption of extended half-life rFVIII products in the United States. Methods We performed a retrospective analysis using the US Specialty Pharmacy Database (2015–2018). Included patients had a diagnosis of hemophilia A, ≥2 consecutive monthly claims for efmoroctocog alfa or rurioctocog alfa pegol for prophylaxis, and weight data. Outcome measures included weekly dosing frequency and dispensed weekly dose. Results The analysis included 774 patients (efmoroctocog alfa, 506; rurioctocog alfa pegol, 268). Mean (SD) age was 24.2 (15.8) and 26.3 (14.9) years for patients receiving efmoroctocog alfa and rurioctocog alfa pegol, respectively; mean (SD) weight was 68.4 (36.8) and 79.8 (37.7) kg, respectively. The most frequent efmoroctocog alfa regimen was twice weekly (45.7%), followed by every 4 days (20.6%), every 3 days (9.1%), and 3 times per week (7.5%). The most frequent rurioctocog alfa pegol regimen was twice weekly (72.4%), followed by 3 times per week (8.7%), every 4 days (7.6%), and every 3 days (5.5%). The proportion of efmoroctocog alfa twice-weekly dispensing records increased from 31.5% to 50.9%, and every 4 days dispensing records decreased from 31.3% to 14.5% (2015–2018). The proportion of rurioctocog alfa pegol dispensing records remained broadly stable (2016–2018). Overall, mean (SD; median) weekly prophylactic dose was 105.4 (77.9; 92.6) IU/kg with efmoroctocog alfa, and 96.8 (41.9; 90.9) IU/kg with rurioctocog alfa pegol. Conclusion In this database study, the most frequently observed dosing frequency was twice weekly for patients receiving efmoroctocog alfa or rurioctocog alfa pegol. The observed mean weekly consumption was slightly higher, and variation was greater, in patients receiving efmoroctocog alfa versus rurioctocog alfa pegol.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States

Wu¹,

Sun²,

Fan³

2022

JBM

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“… 82 , 83 PK studies in pediatric and adult subjects have demonstrated a terminal half-life range of 6–31.9 hours for FVIII-Fc, and 10.9–23.6 hours for FVIII-PEG, and significant variability for other EHL-FVIII PK metrics. 82 , 84 , 85 A report of 38 Finnish adults (74% receiving FVIII-Fc and 26% receiving FVIII-PEG) demonstrated that EHL-FVIII half-life correlates strongly with SHL-FVIII half-life, suggesting that many of the factors that influence PK of SHL products are also important regulators of EHL-FVIII PK. 86 …”

Section: Pharmacokinetics Of Extended Half-life Fviii Productsmentioning

confidence: 99%

Current Understanding of Inherited Modifiers of FVIII Pharmacokinetic Variation

Swystun¹,

Lillicrap²

2023

PGPM

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The inherited bleeding disorder hemophilia A involves the quantitative deficiency of the coagulation cofactor factor VIII (FVIII). Prophylactic treatment of severe hemophilia A patients with FVIII concentrates aims to reduce the frequency of spontaneous joint bleeding and requires personalized tailoring of dosing regimens to account for the substantial inter-individual variability of FVIII pharmacokinetics. The strong reproducibility of FVIII pharmacokinetic (PK) metrics between repeat analyses in the same individual suggests this trait is genetically regulated. While the influence of plasma von Willebrand factor antigen (VWF:Ag) levels, ABO blood group, and patient age on FVIII PK is well established, estimates suggest these factors account for less than 35% of the overall variability in FVIII PK. More recent studies have identified genetic determinants that modify FVIII clearance or half-life including VWF gene variants that impair VWF-FVIII binding resulting in the accelerated clearance of VWF-free FVIII. Additionally, variants in receptors that regulate the clearance of FVIII or the VWF-FVIII complex have been associated with FVIII PK. The characterization of genetic modifiers of FVIII PK will provide mechanistic insight into a subject of clinical significance and support the development of personalized treatment plans for patients with hemophilia A.

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“…5 Extended half-life (EHL) FVIII products offer the opportunity of less frequent infusions and potentially improved compliance, while retaining good bleed control, compared with standard half-life (SHL) FVIII products. [6][7][8][9][10] rVIII-SingleChain (AFSTYLA®; CSL Behring, Marburg, Germany) is a recombinant FVIII (rFVIII) with increased binding affinity to von Willebrand factor (VWF) compared with SHL FVIII concentrates and enhanced molecular stability. 11,12 The AFFINITY clinical trial program has established frequency, and consumption before and after switching to rVIII-SingleChain were recorded.…”

Section: Introductionmentioning

confidence: 99%

A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

Guillet

Hassoun²,

Wibaut³

et al. 2023

Thromb Haemost

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Background rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A. Objectives To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis. Patients/Methods This interim analysis includes data, collected between January 2018 — September 2021, from patients treated with rVIII-SingleChain prophylaxis at French Hemophilia Treatment centers. Data on annualized bleeding rates, dosing frequency, and consumption before and after switching to rVIII-SingleChain were recorded. A population PK analysis was also conducted to estimate PK parameters. Results Overall, 43 patients switched to prophylaxis with rVIII-SingleChain either from a previous prophylaxis regimen or from on-demand treatment. Following the switch to rVIII-SingleChain, patients maintained excellent bleed control. After switching to rVIII-SingleChain, most patients maintained or reduced their regimen. Interestingly, a majority of patients treated >2 ×/weekly with a standard half-life FVIII reduced both injection frequency and FVIII consumption with rVIII-SingleChain. A PK analysis revealed a lower clearance of rVIII-SingleChain (1.9 vs. 2.1 dL/h) and a longer half-life both in adolescents/adults (n = 28) and pediatric (n = 6) patients (15.5 and 11.9 hours, respectively vs. 14.5 and 10.3 hours) than previously reported. Conclusions Patients who switched to rVIII-SingleChain prophylaxis demonstrated excellent bleed control and a reduction in infusion frequency. A population PK analysis revealed improved PK parameters compared with those reported in the clinical trial.

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Extended half‐life factor VIII concentrates in adults with hemophilia A: Comparative pharmacokinetics of two products

Cited by 6 publications

References 23 publications

Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States

Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States

Current Understanding of Inherited Modifiers of FVIII Pharmacokinetic Variation

A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

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