BAY 94‐9027, a PEGylated recombinant factor VIII, exhibits a prolonged half‐life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies

Shah, Anita; Coyle, Thomas; Lalezari, Shadan; Fischer, Kathelijn; Kohlstaedde, B.; Delesen, Heinz; Radke, S.; Michaels, Lisa A.

doi:10.1111/hae.13561

Cited by 31 publications

(34 citation statements)

References 26 publications

(61 reference statements)

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“…Despite differences in reported absolute half‐lives, all studies evaluating the PK of EHL FVIIIs have shown that these various products prolong the half‐life by about 1.4‐fold to 1.6‐fold in comparison to a SHL FVIII (in all cases comparisons have been made with Advate).…”

Section: Discussionmentioning

confidence: 99%

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

Carção

Chelle

Clarke

et al. 2019

Journal of Thrombosis and Haemostasis

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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;

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Section: Discussionmentioning

confidence: 99%

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

Carção

Chelle

Clarke

et al. 2019

Journal of Thrombosis and Haemostasis

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“…Doses were extrapolated from experience in adolescents and adults in the phase 1 and phase 2/3 PROTECT VIII studies. 4,12 Patients received 25-60 IU/kg of BAY 94-9027 at least once per week; initial dosing recommendations were 25 IU/kg twiceweekly, 45 IU/kg every 5 days, or 60 IU/kg every 7 days. Investigators were encouraged to start with the least-frequent regimen that they believed was appropriate for the patient.…”

Section: Methodsmentioning

confidence: 99%

“…BAY 94-9027 has demonstrated an extended half-life (EHL) in children, compared with standard-acting FVIII products. 4,5 In the phase 2/3 PROTECT VIII study, BAY 94-9027 demonstrated effective prophylaxis in adults and adolescents with severe haemophilia A with dosing up to every 7 days. 6 Assessing children as an independent population is necessary because of age-related differences in the pharmacokinetics of all FVIII products, which have a shorter half-life and faster clearance than in older patients.…”

Section: Introductionmentioning

confidence: 99%

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PROTECT VIII Kids: BAY 94‐9027 (PEGylated Recombinant Factor VIII) safety and efficacy in previously treated children with severe haemophilia A

Santagostino

Kenet

Fischer³

et al. 2020

Haemophilia

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Introduction: BAY 94-9027, a site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII) with extended half-life, demonstrated efficacy for bleed prevention and treatment in previously treated adolescents and adults with severe haemophilia A. Aim:To assess BAY 94-9027 in children with severe haemophilia A. Methods:In the two-part PROTECT VIII Kids study, boys <12 years with <1% FVIII and >50 exposure days (EDs) to FVIII were enrolled in two cohorts (<6 years; 6-<12 years) and treated with BAY 94-9027 prophylaxis twice-weekly, every 5 days, or every 7 days at physician discretion for ≥50 EDs (Part 1) or twice-weekly for 12weeks (Part 2). Annualized bleeding rate (ABR) was a primary efficacy endpoint; FVIII inhibitor development was the primary safety variable.Results: At study completion, 25 patients had been treated twice-weekly, 28 in the every-5-day group, and 8 in the every-7-day group. Median ABR for all bleeds was 2.9 (Part 1) and 2.4 (Part 2) and similar in younger and older patients; median ABR for joint bleeds was 0 for both cohorts. In the last 90 days' treatment, median ABR was 0 for younger and older patients (Part 1). Of 149 reported bleeds, 93% were treated with ≤2 infusions. Twelve patients, the majority <6 years (n = 11), discontinued due to apparent loss of efficacy or hypersensitivity. No FVIII inhibitors developed. Conclusions:In PROTECT VIII Kids, which allowed tailoring of prophylaxis to individual clinical response, BAY 94-9027 was efficacious for bleed prevention and treatment in previously treated children with severe haemophilia A. K E Y W O R D Schildren, factor VIII, haemophilia A, polyethylene glycol, prophylaxis e56 |

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“…27 In children, previous studies have shown that FVIII half-life were shorter than those reported in adults receiving the same FVIII product. [28][29][30] However, with the exception of bridging FIXa and FX, emicizumab and FVIII have little in common, and emicizumab pharmacokinetic properties are less likely to be correlated with binding-capacity to VWF or ABO groups, as described recently for FVIII. 31 As a result, same QW, Q2W, and Q4W emicizumab dosing regimens as those used for adults were studied in children with HA.…”

Section: Pharmacology Mode Of Action and Pharmacokinetics Of Emicizmentioning

confidence: 94%

<p>Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A</p>

Quellec¹

2020

DDDT

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Emicizumab is a bispecific, humanized, monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the generation of FXa by FIXa in patients with hemophilia A (HA). This subcutaneous non-factor agent has been recently extensively approved for the prophylaxis of patients of HA patients with and without FVIII-inhibitors of all ages, although few data are currently available in children. In Phase 3 clinical trials and case series, emicizumab prophylaxis significantly reduced bleeding rates compared to previous treatment in HA adolescents and children with or without FVIIIinhibitors and was generally well tolerated. In addition, subcutaneous administration of emicizumab provided beneficial effects on health-related quality of life, and lessened the burden of the disease in HA patients as well as in their caregivers. However, additional prospective studies are required to evaluate the long-term safety of emicizumab prophylaxis in very young patients, including previously untreated patients. The aim of this paper was to review the limited data available on the use of emicizumab prophylaxis in children and to highlight the need for further studies to address remaining concerns.

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BAY 94‐9027, a PEGylated recombinant factor VIII, exhibits a prolonged half‐life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies

Abstract: BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.

Cited by 31 publications

References 26 publications

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

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

PROTECT VIII Kids: BAY 94‐9027 (PEGylated Recombinant Factor VIII) safety and efficacy in previously treated children with severe haemophilia A

<p>Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A</p>

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