Kisunla: which tox species, and why?

“toxicity studies were conducted in cynomolgus monkey (6-week IV donanemab) to assess for any off-target toxicity, and in the PDAPP transgenic mouse model (6-week and 6-month SC mE8c, a murine surrogate) to assess for relevant on-target effects”

“Donanemab is not pharmacologically active in normal rodent or nonrodent; therefore, toxicity studies were conducted in cynomolgus monkey (6-week IV donanemab) to assess for any off-target toxicity”

“These studies used mE8c, the murine analog of donanemab, to avoid immunogenicity that would be expected with donanemab, a humanized antibody, in mouse.”

“toxicity studies were conducted in cynomolgus monkey (6-week IV donanemab) to assess for any off-target toxicity, and in the PDAPP transgenic mouse model (6-week and 6-month SC mE8c, a murine surrogate) to assess for relevant on-target effects”

“Developmental and reproductive toxicity studies were not conducted based on the age of the indicated population.”

“Carcinogenicity studies of donanemab were not conducted because its target, human AβN3pE-x peptide, is not present in wild-type rodents, and carcinogenicity studies in transgenic rodents are not feasible.”

“These studies used mE8c, the murine analog of donanemab, to avoid immunogenicity that would be expected with donanemab, a humanized antibody, in mouse. In the pivotal (GLP) studies, mE8c was administered to 12- to 15-month-old PDAPP mice weekly for 6 weeks (0, 10, 30, or 100 mg/kg SC) or 5 months (0, 30, or 100 mg/kg SC).”