• A Tiede, B Brand, R Fischer, K Kavakli, S R Lentz, T Matsushita, C Rea, K Knobe, and D Viuff.
• Hannover Medical School, Hannover, Germany. Tiede.Andreas@mh-hannover.de
• J. Thromb. Haemost. 2013 Apr 1; 11 (4): 670-8.

BackgroundN8-GP is a recombinant factor VIII (FVIII) with a site-directed glycoPEGylation for the purpose of half-life prolongation.ObjectivesTo evaluate the safety and pharmacokinetic profiles of N8-GP in comparison with those of the patients' previous FVIII products.Patients/MethodsThis dose-escalation trial included previously treated patients with severe hemophilia A who received one of three dose levels (25, 50 or 75 U kg(-1) ) of N8-GP and FVIII product. Each dose escalation was preceded by safety and pharmacokinetic assessment. The trial was registered at www.clinicaltrials.gov (NCT01205724).ResultsTwenty-six patients each received one dose of their previous FVIII product followed by the same, single dose of N8-GP. N8-GP, at any tested dose, was well tolerated, with a low frequency of adverse events. No new inhibitors against FVIII or N8-GP and no binding antibodies against N8-GP developed during the trial. The pharmacokinetics of N8-GP were dose-linear. The incremental recovery of N8-GP was 0.025 [(U mL(-1) )/(U kg(-1) )]. The clearance was 1.79 mL(-1)  h(-1)  kg(-1) . The estimated time from dosing of 50 U kg(-1) N8-GP to a plasma activity of 1% was 6.5 days (range: 3.6-7.9 days). The mean terminal half-life of N8-GP was 19.0 h (range: 11.6-27.3 h), 1.6-fold longer than that of the patients' previous products.ConclusionsA single dose of up to 75 U kg(-1) N8-GP was well tolerated in patients with hemophilia A, with no safety concerns. N8-GP had a prolonged half-life, and FVIII:C activity remained at > 1% for longer than the patient's previous product. These results indicate that N8-GP has the potential to reduce dosing frequency during prophylaxis.© 2013 International Society on Thrombosis and Haemostasis.

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