Dupixent: which tox species, and why?

“three pivotal repeat dose toxicity studies and an enhanced pre- and postnatal developmental toxicity study (ePPND) in cynomolgus monkey with REGN646 which is a fully human homologous antibody specific for cynomolgus monkey IL4Rα, and a subcutaneous fertility study in mice with REGN1103, a mouse homologous antibody that binds to IL4Rα.”

“Because dupilumab does not cross-react with species used to evaluate nonclinical safety, the sponsor developed a fully human homologous antibody, REGN646,”

“three pivotal repeat dose toxicity studies and an enhanced pre- and postnatal developmental toxicity study (ePPND) in cynomolgus monkey with REGN646 which is a fully human homologous antibody specific for cynomolgus monkey IL4Rα, and a subcutaneous fertility study in mice with REGN1103, a mouse homologous antibody that binds to IL4Rα.”

“The three pivotal repeat dose toxicity studies, including a 5-week intravenous infusion (IV), a 13-week subcutaneous (SC) and a 6-month IV and SC studies, were conducted with REGN646 in peripubertal adolescent cynomolgus monkeys”

“A subcutaneous fertility study in young sexually mature male and female mice with REGN1103 and an enhanced pre- and postnatal developmental toxicity study (ePPND) in cynomolgus monkeys with REGN646 were reviewed under IND 107969.”

“No carcinogenicity studies were conducted with dupilumab or homologous monoclonal antibodies REGN646 and REGN1103 in any species.”

“The sponsor submitted three pivotal repeat dose toxicity studies and an enhanced pre- and postnatal developmental toxicity study (ePPND) in cynomolgus monkey with REGN646 which is a fully human homologous antibody specific for cynomolgus monkey IL4Rα, and a subcutaneous fertility study in mice with REGN1103, a mouse homologous antibody that binds to IL4Rα.”