Spevigo: genotox, carcinogenicity and repro: done or skipped?

“Genotoxicity and stand-alone safety pharmacology studies were not conducted.”

“there are no concrete reasons to believe that inhibition of IL36R by spesolimab would lead to carcinogenicity. The Executive Carcinogenicity Assessment committee (ECAC) concurred with this conclusion.”

“The maternal and developmental NOAELs were both 50 mg/kg/dose.”

“However, no treatment-related organ toxicities or clinical signs indicative of respiratory or neurobehavioral effects were observed in mice after intravenous administration of the surrogate antibody BI 674304 for up to 26 weeks”

“No genotoxicity studies have been performed with spesolimab. This is considered acceptable as monoclonal antibodies are unlikely to interact directly with DNA or other chromosomal material (see SmPC section 5.3).”

“No genotoxicity studies have been performed with spesolimab. This is considered acceptable as monoclonal antibodies are unlikely to interact directly with DNA or other chromosomal material (see SmPC section 5.3).”

“No genotoxicity studies have been performed with spesolimab. This is considered acceptable as monoclonal antibodies are unlikely to interact directly with DNA or other chromosomal material (see SmPC section 5.3).”

“Regarding carcinogenesis, based on data from the 6-month general toxicity study of BI 674304 in mice, scientific literature on the potential role of IL36R in tumor promotion, and clinical data from spesolimab clinical trials, there are no concrete reasons to believe that inhibition of IL36R by spesolimab would lead to carcinogenicity.”

“there are no concrete reasons to believe that inhibition of IL36R by spesolimab would lead to carcinogenicity. The Executive Carcinogenicity Assessment committee (ECAC) concurred with this conclusion.”

“Stand-alone safety pharmacology studies were not conducted. Safety pharmacology studies were not embedded in the repeat-dose toxicity studies.”