TY - JOUR
T1 - Clinical evaluation of moroctocog alfa (AF-CC), a new generation of B-domain deleted recombinant factor VIII (BDDrFVIII) for treatment of haemophilia A
T2 - Demonstration of safety, efficacy, and pharmacokinetic equivalence to full-length recombinant factor VIII
AU - Recht, Michael
AU - Nemes, L.
AU - Matysiak, M.
AU - Manco-Johnson, M.
AU - Lusher, J.
AU - Smith, M.
AU - Mannucci, P.
AU - Hay, C.
AU - Abshire, T.
AU - O'Brien, A.
AU - Hayward, B.
AU - Udata, C.
AU - Roth, D. A.
AU - Arkin, S.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - BDDrFVIII is a B-domain deleted recombinant factor VIII (rFVIII) product for haemophilia A. Manufacture uniquely includes purification chromatography by synthetic-affinity ligand rather than murine-based monoclonal antibody, as well as an albumin-free cell culture process. BDDrFVIII was studied in 204 patients, including 62 subjects <16years old, in two studies. A double-blind, randomized, pharmacokinetic (PK) crossover study, utilizing a central laboratory assay (one-stage (OS)) for both drug potency assignment and plasma FVIII-activity measurements, demonstrated that BDDrFVIII was PK-equivalent to a full-length rFVIII. Favourable efficacy and safety were observed: during defined routine prophylaxis in a patient population significant for preexisting target joints, nearly half (45.7%) of patients had no bleeding, and a low-annualized bleed rate (ABR) was achieved (median 1.9); 92.5% of haemorrhages (n = 187) required ≤2 infusions. Three subjects (1.5%, across both studies) developed de novo inhibitors (low-titre, transient), and the primary safety endpoint, based on a prospective Bayesian analysis, demonstrated the absence of neoantigenicity for BDDrFVIII. The PK-equivalence, based on central testing to align test and reference articles, and the novel Bayesian analysis of inhibitor safety in these investigations reflect robust experimental designs with relevance to future studies. This extensive dataset demonstrates the safety and efficacy of BDDrFVIII for haemophilia A.
AB - BDDrFVIII is a B-domain deleted recombinant factor VIII (rFVIII) product for haemophilia A. Manufacture uniquely includes purification chromatography by synthetic-affinity ligand rather than murine-based monoclonal antibody, as well as an albumin-free cell culture process. BDDrFVIII was studied in 204 patients, including 62 subjects <16years old, in two studies. A double-blind, randomized, pharmacokinetic (PK) crossover study, utilizing a central laboratory assay (one-stage (OS)) for both drug potency assignment and plasma FVIII-activity measurements, demonstrated that BDDrFVIII was PK-equivalent to a full-length rFVIII. Favourable efficacy and safety were observed: during defined routine prophylaxis in a patient population significant for preexisting target joints, nearly half (45.7%) of patients had no bleeding, and a low-annualized bleed rate (ABR) was achieved (median 1.9); 92.5% of haemorrhages (n = 187) required ≤2 infusions. Three subjects (1.5%, across both studies) developed de novo inhibitors (low-titre, transient), and the primary safety endpoint, based on a prospective Bayesian analysis, demonstrated the absence of neoantigenicity for BDDrFVIII. The PK-equivalence, based on central testing to align test and reference articles, and the novel Bayesian analysis of inhibitor safety in these investigations reflect robust experimental designs with relevance to future studies. This extensive dataset demonstrates the safety and efficacy of BDDrFVIII for haemophilia A.
KW - BDDrFVIII
KW - Factor VIII
KW - Haemophilia
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=67649855138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649855138&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2516.2009.02027.x
DO - 10.1111/j.1365-2516.2009.02027.x
M3 - Article
C2 - 19473411
AN - SCOPUS:67649855138
SN - 1351-8216
VL - 15
SP - 869
EP - 880
JO - Haemophilia
JF - Haemophilia
IS - 4
ER -