TY - JOUR
T1 - PROLONG-9FP clinical development program-phase i results of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP)
AU - Santagostino, Elena
PY - 2013/3
Y1 - 2013/3
N2 - Hemophilia B is a severe bleeding disorder that is characterized by a deficiency or dysfunction of coagulation factor IX (FIX). Replacement therapy using recombinant or plasma-derived FIX is available, but the relatively short half-life of FIX (approximately 18 hours) necessitates administration every 2-3 days to prevent bleeding episodes. A recombinant fusion protein linking coagulation factor IX with albumin, known as rIX-FP, was developed to extend the half-life of recombinant FIX and allow for less frequent dosing. In a phase I, multicenter, dose-escalation trial (PROLONG-9FP), the safety and pharmacokinetics of rIX-FP were assessed in patients with hemophilia B. At a dose of 25-75 IU/kg, rIX-FP was well tolerated: no serious adverse events were reported and there was no evidence of hypersensitivity or immunogenic reactions. Pharmacokinetic analysis indicated enhanced properties, including a 5-fold increase in half-life, 44% higher recovery, 7-fold greater area under the curve, and 7-fold slower clearance, compared with recombinant FIX. Trough levels were maintained above 5% after 7 days when rIX-FP was administered at 25 IU/kg and after 14 days when given at 50 IU/kg, suggesting that schedules involving weekly dosing or dosing every 2 weeks are feasible. These results represent the first reported experience with rIX-FP in humans, and suggest that rIX-FP therapy is feasible and well tolerated in patients with hemophilia B. Phase II/III studies evaluating rIX-FP are underway.
AB - Hemophilia B is a severe bleeding disorder that is characterized by a deficiency or dysfunction of coagulation factor IX (FIX). Replacement therapy using recombinant or plasma-derived FIX is available, but the relatively short half-life of FIX (approximately 18 hours) necessitates administration every 2-3 days to prevent bleeding episodes. A recombinant fusion protein linking coagulation factor IX with albumin, known as rIX-FP, was developed to extend the half-life of recombinant FIX and allow for less frequent dosing. In a phase I, multicenter, dose-escalation trial (PROLONG-9FP), the safety and pharmacokinetics of rIX-FP were assessed in patients with hemophilia B. At a dose of 25-75 IU/kg, rIX-FP was well tolerated: no serious adverse events were reported and there was no evidence of hypersensitivity or immunogenic reactions. Pharmacokinetic analysis indicated enhanced properties, including a 5-fold increase in half-life, 44% higher recovery, 7-fold greater area under the curve, and 7-fold slower clearance, compared with recombinant FIX. Trough levels were maintained above 5% after 7 days when rIX-FP was administered at 25 IU/kg and after 14 days when given at 50 IU/kg, suggesting that schedules involving weekly dosing or dosing every 2 weeks are feasible. These results represent the first reported experience with rIX-FP in humans, and suggest that rIX-FP therapy is feasible and well tolerated in patients with hemophilia B. Phase II/III studies evaluating rIX-FP are underway.
KW - Albumin fusion protein
KW - Factor IX
KW - Hemophilia B
KW - PROLONG-9FP
KW - Recombinant albumin
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UR - http://www.scopus.com/inward/citedby.url?scp=84875522099&partnerID=8YFLogxK
U2 - 10.1016/S0049-3848(13)70151-8
DO - 10.1016/S0049-3848(13)70151-8
M3 - Article
C2 - 23537724
AN - SCOPUS:84875522099
VL - 131
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - SUPPL.2
ER -