Gamifant: which tox species, and why?

“In in vitro studies, emapalumab (NI-0501) bound to human (hIFNγ) and cynomolgus monkey IFNγ with similar affinity, but did not bind to rodent IFNγ, supporting the use of cynomolgus monkeys as the single pharmacologically relevant species for toxicity assessment.”

“Emapalumab was cross-reactive to both cynomolgus and rhesus monkey, but no binding was detected in the dog, rat, or mouse.”

“The Applicant characterized a commercially available rat IgG1 anti-mouse IFNγ monoclonal antibody (mAb), XMG1.2, and used it as a surrogate of emapalumab to conduct studies in murine HLH models, as well as in their assessments of potential effects on embryofetal development.”

“The Applicant evaluated the safety of emapalumab in GLP-compliant repeat-dose toxicology studies in cynomolgus monkeys.”

“Standalone fertility assessments were not conducted as they are not needed to support the marketing of this product for the intended treatment indication. No adverse effects on male or female reproductive organs were observed in the repeat-dose toxicity studies in cynomolgus monkeys. Embryo-fetal developmental toxicology studies were conducted in mice, with XMG1.2 used as surrogate for emapalumab.”

“No carcinogenicity studies were conducted with emapalumab as per International Conference on Harmonisation S6.”

“The Applicant characterized a commercially available rat IgG1 anti-mouse IFNγ monoclonal antibody (mAb), XMG1.2, and used it as a surrogate of emapalumab to conduct studies in murine HLH models, as well as in their assessments of potential effects on embryofetal development.”