BIOMAT Database Logo BIOMAT Database Logo

Cases of less-than-expected FVIII activity in previously treated patients during post-marketing surveillance of N8-GP. 2023

Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Institute for Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany.

BACKGROUND Turoctocog alfa pegol (N8-GP) is a glycoPEGylated, extended half-life (EHL), human recombinant factor VIII (FVIII) approved for the treatment and prevention of bleeding episodes in patients with haemophilia A. Since its launch in August 2019, > 800 patients have been treated worldwide. OBJECTIVE To present data from identified post-marketing cases of less-than-expected FVIII activity in previously treated patients (PTPs) without inhibitors after switching to N8-GP. METHODS The post-marketing safety database was searched using keywords such as 'coagulation FVIII level decreased'. Identified cases reported prior to 13 October 2021 were included in this report. Cases in which patients had FVIII inhibitors were excluded. RESULTS Here we report 14 cases of less-than-expected FVIII activity. Details varied greatly amongst the cases. At presentation, FVIII activity ranged from 1% (15 min post-dose) to 51% (2 days post-dose). Seven patients experienced bleeding episodes after switching to N8-GP with heterogeneity in bleeding presentations. Six out of seven patients who were tested for anti-PEG IgG and/or IgM antibodies were positive. In all known cases, FVIII activity returned to the expected range when switched to an alternative FVIII replacement product. CONCLUSIONS In conclusion, the 14 reported cases of less-than-expected FVIII activity, without presence of detectable FVIII inhibitors, presented with heterogenous characteristics, and wide variations in FVIII activity and anti-PEG antibody titre. FVIII activity returned to the expected range after switching to alternative FVIII products. In line with WFH guidelines, monitoring of FVIII activity can ensure FVIII activity in the expected range. The safety surveillance of N8-GP continues.

UI MeSH Term Description Entries
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D011358 Product Surveillance, Postmarketing Surveillance of drugs, devices, appliances, etc., for efficacy or adverse effects, after they have been released for general sale. Drug Surveillance, Postmarketing,Evaluation Studies, Postmarketing,Postmarketing Product Surveillance,Product Surveillance, Post-Marketing,Drug Surveillances, Postmarketing,Evaluation Study, Postmarketing,Post-Marketing Product Surveillance,Post-Marketing Product Surveillances,Postmarketing Drug Surveillance,Postmarketing Drug Surveillances,Postmarketing Evaluation Studies,Postmarketing Evaluation Study,Postmarketing Product Surveillances,Product Surveillance, Post Marketing,Product Surveillances, Post-Marketing,Product Surveillances, Postmarketing,Studies, Postmarketing Evaluation,Study, Postmarketing Evaluation,Surveillance, Post-Marketing Product,Surveillance, Postmarketing Drug,Surveillance, Postmarketing Product,Surveillances, Post-Marketing Product,Surveillances, Postmarketing Drug,Surveillances, Postmarketing Product
D005169 Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Coagulation Factor VIII,Factor VIII Clotting Antigen,Factor VIII Coagulant Antigen,Factor VIII Procoagulant Activity,Thromboplastinogen,Blood Coagulation Factor VIII,F VIII-C,Factor 8,Factor 8 C,Factor Eight,Factor VIIIC,Hyate-C,Hyatt-C,F VIII C,Hyate C,HyateC,Hyatt C,HyattC
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages
D006490 Hemostatics Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure. Antihemorrhagic,Hemostatic,Antihemorrhagics
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5.
September 2020, Journal of thrombosis and haemostasis : JTH,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Osteoporosis--less than expected in patients with scleroderma?
July 2000, The Journal of rheumatology,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model.
November 2013, Haemophilia : the official journal of the World Federation of Hemophilia,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Illustrative Cases from the Pathfinder Clinical Trials of Patients with Hemophilia A Treated with Turoctocog Alfa Pegol (N8-GP).
January 2021, Patient preference and adherence,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Measuring factor VIII activity in samples from patients treated with N8-GP (Esperoct® ; turoctocog alfa pegol) during the pathfinder clinical trials programme.
May 2021, Haemophilia : the official journal of the World Federation of Hemophilia,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
The safety and efficacy of N8-GP (turoctocog alfa pegol) in previously untreated pediatric patients with hemophilia A.
February 2023, Blood advances,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Post-marketing surveillance should include effects during pregnancy.
February 2005, BMJ (Clinical research ed.),
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Turoctocog alfa pegol (N8-GP) in severe hemophilia A: Long-term safety and efficacy in previously treated patients of all ages in the pathfinder8 study.
February 2022, Research and practice in thrombosis and haemostasis,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
Long-term safety and efficacy of N8-GP in previously treated adults and adolescents with hemophilia A: Final results from pathfinder2.
September 2020, Journal of thrombosis and haemostasis : JTH,
Johannes Oldenburg, and Gary Benson, and Pratima Chowdary, and Susan Halimeh, and Tadashi Matsushita, and Anne Nørland, and Mohd Nawi Wahid, and Laszlo Nemes
A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models.
March 2013, Blood,
Copied contents to your clipboard!