Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina; Lepatan, Lynda Mae; Skotnicki, Aleksander B.; Boggio, Lisa; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross; Fischer, Kathelijn; Gill, Joan Cox; P'ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, L.; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; Ledger, Katie St.; Pabinger, Ingrid

doi:10.1182/blood-2016-01-687434

Cited by 78 publications

(159 citation statements)

References 23 publications

(36 reference statements)

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…In addition, 73.8% of patients remained bleed-free (83.1% free of spontaneous bleeds) during personalized prophylaxis with Nuwiq â in the NuPreviq study. This compares with 45% of patients in the rFVIII-Fc study [19], 39.6% of patients treated with full-length pegylated rFVIII [35], and 43% of patients treated with single-chain rFVIII [36], in studies of a similar duration, and 26.5% of patients treated with full-length rFVIII in a 1-year study [10].…”

Section: Discussionmentioning

confidence: 84%

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

Lissitchkov

Rusen²,

Georgiev

et al. 2017

Haemophilia

View full text Add to dashboard Cite

Introduction: Nuwiq â (human-cl rhFVIII) is a 4 th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq â in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two-or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1. .1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg À1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion: PK-guided personalized prophylaxis with Nuwiq â provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.

show abstract

Section: Discussionmentioning

confidence: 84%

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

Lissitchkov

Rusen²,

Georgiev

et al. 2017

Haemophilia

View full text Add to dashboard Cite

show abstract

“…In the AFFINITY clinical trial program, rFVIII-SC showed excellent hemostatic efficacy with a median annualized bleeding rate (ABR) of 1.14 that is comparable to other recently approved factor products 8. For example, rFVIII-Fc (Eloctate) reported a median ABR of 1.6, and simoctocog alfa (Nuwiq) reported a median ABR of 0.9.…”

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

confidence: 96%

“…Moreover, the enhanced affinity for VWF may accelerate the formation of VWF:FVIII complex that not only increases the half-life but also may result in decreased immunogenicity by inhibiting endocytosis of FVIII by dendritic cells 25,26. These modifications resulted in a FVIII molecule with an increased half-life that is comparable to the PEGylated EHL product (Adynovate) 8,10,27,28. When FVIII is normally activated, the heavy and light chains are cleaved and released from VWF.…”

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

confidence: 99%

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

Lieuw¹

2017

JBM

View full text Add to dashboard Cite

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.

show abstract

“…The first trial [37] included PTPs with severe hemophilia A 12 years. Participants were allocated to receive either on-demand (n = 27) or prophylactic (n = 146) treatment with rFVIII-SingleChain.…”

Section: Rfviii-singlechainmentioning

confidence: 99%

Extended Half-Life Factor VIII and Factor IX Preparations

Graf¹

2018

Transfus Med Hemother

View full text Add to dashboard Cite

In the last couple of years, several extended half-life factor VIII and factor IX preparations were intensively studied and gained approval. In order to extend half-lives, techniques like fusion to protein conjugates (Fc part of IgG₁ or albumin), chemical modification (PEGylation), and protein sequence modification are implemented. With these techniques, it is possible to extend half-lives of factor IX products 4- to 6- fold, while half-life extension of factor VIII products is limited to 1.5- to 2-fold due to their interaction with von Willebrand factor. Nevertheless, both extended half-life factor VIII and IX products have improved and facilitated prophylactic factor replacement therapy in hemophilia A and B, respectively. Extended half-life factor concentrates pose challenges to coagulation laboratories because accurate therapy monitoring is not possible with all factor activity assays currently used.

show abstract

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Abstract: Key Points rVIII-SingleChain is a novel rFVIII, designed to have high stability and high binding affinity for VWF. In severe hemophilia A patients, rVIII-SingleChain was well tolerated and resulted in low bleeding rates, when dosed twice per week.

Cited by 78 publications

References 23 publications

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

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

Extended Half-Life Factor VIII and Factor IX Preparations

Contact Info

Product

Resources

About

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Abstract: Key Points rVIII-SingleChain is a novel rFVIII, designed to have high stability and high binding affinity for VWF. In severe hemophilia A patients, rVIII-SingleChain was well tolerated and resulted in low bleeding rates, when dosed twice per week.

Cited by 78 publications

References 23 publications

PK‐guided personalized prophylaxis with Nuwiq® (human‐cl rhFVIII) in adults with severe haemophilia A

PK‐guided personalized prophylaxis with Nuwiq® (human‐cl rhFVIII) in adults with severe haemophilia A

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

Extended Half-Life Factor VIII and Factor IX Preparations

Contact Info

Product

Resources

About

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A