Vabysmo: what was done before first-in-human, and what came after?

“The following studies were reviewed under the initial IND by Dr Lansita (9-23- 2013).  Study # 1053361, 2-Month Toxicity and Toxicokinetic Study with RO6867461 following Intravitreous and Intravenous Administration in Cynomolgus Monkeys with a 4-Week Recovery Phase”

“The proposed clinical starting dose of 0.5 mg/eye is supported by the nonclinical data but the high dose of 6.0 mg/eye is not.”

“Study # 8292406, 26-Week Partial Ascending-Dose Toxicity and Toxicokinetic Study Following Once Monthly Intravitreous Injections in Cynomolgus Monkeys with a 13-Week Recovery”

“Study # 1053361, 2-Month Toxicity and Toxicokinetic Study with RO6867461 Following Intravitreous and Intravenous Administration in Cynomolgus Monkeys with a 4-Week Recovery Phase”

“A pre- and postnatal development study could not be conducted in cynomolgus monkeys due to ADA formation and exposure loss observed in general toxicology studies preventing sufficient systemic exposure with faricimab in such a study.”

“An embryofetal development (EFD) study in cynomolgus monkeys showed an increase incidence of abortions in faricimab treated monkeys at IV doses of 1 or 3 mg/kg administered weekly on gestation days 20 to 48.”

“A pre- and postnatal development study could not be conducted in cynomolgus monkeys due to ADA formation and exposure loss observed in general toxicology studies preventing sufficient systemic exposure with faricimab in such a study.”

“No standard rodent carcinogenicity studies have been conducted as faricimab showed no relevant binding to mouse or rat VEGF-A.”

“No standard rodent carcinogenicity studies have been conducted as faricimab showed no relevant binding to mouse or rat VEGF-A.”

“No standard rodent carcinogenicity studies have been conducted as faricimab is not fully cross-reactive in rodents. The intended anti-angiogenic effects of faricimab and the weight of evidence do not suggest a carcinogenic potential of faricimab.”