Bringing new therapy options to the hemophilia community

Bensen-Kennedy, Debra

doi:10.1016/s0049-3848(13)70153-1

Cited by 4 publications

(7 citation statements)

References 13 publications

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“…Further support is provided by experiments using FVIII-deficient mouse models to assess the activation of rVIII-SingleChain by thrombin, which indicate that rVIII-SingleChain has similar biological activity to that of full-length rFVIII [5]. It also has similar efficacy in reducing blood loss during tail-tip bleeding in mouse models [10]. Lastly, analysis of posttranslational N-glycosylation of rVIII-SingleChain using high-pH anion exchange chromatography showed a pattern that is similar to that seen in other FVIII proteins that are expressed in CHO cells [11].…”

Section: Preclinical Profile Of Rviii-singlechainmentioning

confidence: 97%

“…The AFFINITY clinical trial program was designed as a large interconnected series of Phase I/III studies to evaluate the efficacy, safety, and PK of rVIII-SingleChain. Participants include previously treated adults, adolescents, or children aged 12-65 years with severe hemophilia A [10]. The first phase of the program is divided into three parts, followed by a Phase III pediatric trial and an extension trial.…”

Section: The Affinity Clinical Trial Program: Designmentioning

confidence: 99%

“…In Part 3, additional patients, including adolescents (12 to <18 years) and adults (18-65 years) who were receiving rVIII-SingleChain as on-demand or prophylactic treatment were included to provide a larger dataset for efficacy and safety analyses, with a subset of these patients also undergoing a single-dose PK assessment, as required by the European Medicines Agency [10]. A subgroup analysis of 13 participants who underwent elective surgery was included in the study design so that data could be collected on rVIII-SingleChain efficacy in the challenging perioperative setting [13].…”

Section: Affinity Study In Adults and Adolescentsmentioning

confidence: 99%

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The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII

Pabinger‐Fasching

2016

Thrombosis Research

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For patients with hemophilia A, replacement of deficient factor VIII (FVIII) using plasma-derived or recombinant FVIII (rFVIII) products to restore hemostatic control can reduce bleeding complications and preserve musculoskeletal function. Despite the clinical availability of several of these products, challenges remain in the treatment of hemophilia A, the most notable of which are the risk of inhibitor development and the limited half-life of existing FVIII concentrates, which can make prophylaxis burdensome for patients. The use of recombinant protein technology may lead to novel FVIII products with improved properties. This article describes the story of a unique recombinant FVIII protein, rVIII-SingleChain, which is currently in development. In contrast to native FVIII and other commercially available rFVIII preparations, rVIII-SingleChain uses a strong, covalent bond to connect the light and heavy chains, thereby creating a stable, single-chain rFVIII. It has enhanced intrinsic stability, better integrity after reconstitution, and a higher binding affinity to von Willebrand factor. The physicochemical profile of rVIII-SingleChain and preclinical data on its activity and phamacokinetics strengthened the rationale for its clinical investigation. Available data from the AFFINITY clinical trial program are promising; indicating that it has good hemostatic efficacy when used on demand, for prophylaxis, and in the surgical setting, and is also very well tolerated. A pediatric study and an extension study are ongoing as part of the AFFINITY program.

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Section: Preclinical Profile Of Rviii-singlechainmentioning

confidence: 97%

Section: The Affinity Clinical Trial Program: Designmentioning

confidence: 99%

Section: Affinity Study In Adults and Adolescentsmentioning

confidence: 99%

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The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII

Pabinger‐Fasching

2016

Thrombosis Research

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“…Normally, FVIII is composed of a heavy and a light chain held together by a labile metal ion bridge. CSL Behring developed a BDD recombinant FVIII molecule in which the heavy and light chains are covalently linked that has a twofold increased affinity to VWF 7,23. The increased stability provided by the single-chain covalent bond permits a higher efficiency manufacturing of the full-length factor and results in a more stable protein after reconstitution 24.…”

Section: Current Factors Available and Extended Half-life (Ehl) Factomentioning

confidence: 99%

“…Recently, a novel single-chain recombinant FVIII (Afstyla ® ) has been approved by the US Food and Drug Administration (US FDA) in May 2016. Recombinant factor VIII single chain (rFVIII-SC) has increased stability and affinity for VWF, extending its half-life with the possibility of decreased immunogenicity 7–11…”

Section: Introductionmentioning

confidence: 99%

Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?

Lieuw¹

2017

JBM

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Hemophilia A (HA) is a common bleeding disorder caused by the deficiency of factor VIII (FVIII) with an incidence of ~1 in 5000 male births. Replacement of FVIII is necessary to prevent and treat bleeding episodes. However, with multiple new drugs in addition to old standards, choosing among the different FVIII treatment options is harder than ever. There are FVIII products that are plasma derived or recombinant, FVIII products designed to extend the half-life of FVIII, and the first single-chain FVIII product, recombinant factor VIII single chain (rFVIII-SC). As development of inhibitors to FVIII continues to be a major problem in the care of HA patients, recent studies showing lower rates of inhibitor development with plasma-derived FVIIII products versus recombinant FVIII products have made choosing among the many options now available even more complex. Although still unproven, extended half-life (EHL) products may provide the hope of decreased immunogenicity but need further testing in previously untreated patients (PUPs). This review highlights some of the differences between FVIII products currently available and hopefully assists the clinician to decide which FVIII product to choose for their patients.

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Koncentraty czynników krzepnięcia o przedłużonym działaniu w leczeniu hemofilii

Klukowska¹,

Zawilska

2015

Acta Haematologica Polonica

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Bringing new therapy options to the hemophilia community

Cited by 4 publications

References 13 publications

The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII

The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII

Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?

Koncentraty czynników krzepnięcia o przedłużonym działaniu w leczeniu hemofilii

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