Submitted March 7, 2006
Accepted July 18, 2006
Prolonged bleeding-free period following prophylactic infusion of recombinant factor VIII (Kogenate® FS) reconstituted with pegylated liposomes
Jack Spira*, Olga P. Plyushch, Tatyana A. Andreeva, and Yury Andreev
Recoly N.V. Curacao, Netherlands Antilles
Center for Hematological Research, The Russian Academy of Medical Sciences, Moscow, Russia
Republic Haemophilia Center, St. Petersburg, Russia
Reconstructive Orthopedic Surgery Department, Moscow, Russia
* Corresponding author; email: jack.spira{at}telia.com.
Prophylactic treatment for haemophilia A involves infusion of FVIII concentrates every 2-3 days. Liposomes can be an efficacious vehicle for medicines, and surface modification by PEGylation can prolong liposome circulation time. When reconstituted with PEGylated liposomes (PEGLip), recombinant FVIII (Kogenate® FS; rFVIII-FS) binds non-covalently but with high affinity to the external liposome surface. This preparation showed prolongation of FVIII half life and increased protection from bleeding in preclinical models. Here we report a blinded, controlled, cross-over, multi-center clinical study that evaluated the time free from bleeding episodes in patients with haemophilia A during prophylaxis with standard rFVIII-FS (no liposomes) or PEGLip rFVIII-FS (PEGLip reconstituted) at 25 and 35 IU kg-1 doses. Of 24 enrolled patients, 23 were eligible for efficacy analysis. Mean number of days without bleeds was 7.2± 1.7 with standard rFVIII-FS compared to 13.3± 4.8 with PEGLip rFVIII-FS for the 35 IU kg-1 dose and 5.9± 1.7 with standard rFVIII-FS vs 10.9± 2.9 with PEGLip rFVIII-FS at the 25 IU kg-1 dose (P0.05 between treatment groups for each dose). PEGLip rFVIII-FS was well tolerated. These data suggest that reconstitution of rFVIII-FS with PEGLip may reduce the frequency of treatment during prophylaxis by extending the period between bleeding episodes.
