@article{6b9f470f1cfa445aae429798ea2f9bab,
title = "Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects",
abstract = "In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.",
keywords = "drug safety, ectodermal dysplasia, ectodysplasin A, immunogenicity, prenatal therapy, protein replacement",
author = "Iris K{\"o}rber and Klein, {Ophir D.} and Patrick Morhart and Florian Faschingbauer and Grange, {Dorothy K.} and Angus Clarke and Christine Bodemer and Silvia Maitz and Kenneth Huttner and Neil Kirby and Caroline Durand and Holm Schneider",
note = "Funding Information: This study was funded by the Forberg Foundation (grant 9‐2018 to H.S.) and by Edimer Pharmaceuticals, the sponsor of both clinical trials reported here. Most of the work was performed by I.K. in fulfilment of the requirements for obtaining the degree Dr. med. from the Friedrich‐Alexander‐Universit{\"a}t Erlangen‐N{\"u}rnberg. The authors thank Pascal Schneider (University of Lausanne, Switzerland) and James Maynard (Community Research, Cincinnati, OH, USA) for expert advice and Michael Benson (Charles River Laboratories) for continuous technical support. Three of the authors of this publication are members of the European Reference Network (ERN) Skin, project ID number 739543. Funding Information: This study was funded by the Forberg Foundation (grant 9-2018 to H.S.) and by Edimer Pharmaceuticals, the sponsor of both clinical trials reported here. Most of the work was performed by I.K. in fulfilment of the requirements for obtaining the degree Dr. med. from the Friedrich-Alexander-Universit?t Erlangen-N?rnberg. The authors thank Pascal Schneider (University of Lausanne, Switzerland) and James Maynard (Community Research, Cincinnati, OH, USA) for expert advice and Michael Benson (Charles River Laboratories) for continuous technical support. Three of the authors of this publication are members of the European Reference Network (ERN) Skin, project ID number 739543. Publisher Copyright: {\textcopyright} 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/bcp.14301",
language = "English",
volume = "86",
pages = "2063--2069",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
number = "10",
}