Details

Autor(en) / Beteiligte

• Konkle, Barbara A.
• Stasyshyn, Oleksandra
• Chowdary, Pratima
• Bevan, David H.
• Mant, Tim
• Shima, Midori
• Engl, Werner
• Dyck-Jones, Jacqueline
• Fuerlinger, Monika
• Patrone, Lisa
• Ewenstein, Bruce
• Abbuehl, Brigitt

Titel

Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A

Ist Teil von

• Blood, 2015-08, Vol.126 (9), p.1078-1085

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX 855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX 855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX 855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX 855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A. The trials were registered at www.clinicaltrials.gov as #NCT01736475 and #NCT01599819. •BAX 855, a pegylated full-length rFVIII with extended half-life, was highly effective in the prevention and treatment of bleeding events.•No subjects receiving BAX 855 developed FVIII inhibitory antibodies nor experienced unexpected adverse events.