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

“SAM was negative in a complete and adequate battery of genetic toxicology assays.”

“SAM is also non-carcinogenic as it did not induce tumors in male and female rats administered SAM for up to 95 weeks at exposures which are approximately 32 and 237 times the MRHD based on AUC, respectively and did not induce tumors in rasH2 transgenic mice administered SAM for 6-months.”

“SAM administration to pregnant rats during the period of organogenesis resulted in decreased fetal weights, increased skeletal variations, and a slight increase in total malformations at doses that were maternally toxic and greater than 248 times the MRHD based on AUC.”

“In safety pharmacology studies, SAM and metabolite RDC-9986 were not significant hERG channel blockers, and SAM did not have any significant adverse effects on cardiovascular or respiratory parameters in dogs at doses which are 20 times the maximum recommended human dose (MRHD) of 10 mg SAM based on AUC.”

“No evidence of genotoxicity of samidorphan was found in the in vitro Ames bacterial reverse mutation test, the in vitro chromosome aberration assay in human peripheral blood lymphocytes or in the in vivo mouse bone marrow micronucleus assay.”

“No evidence of genotoxicity of samidorphan was found in the in vitro Ames bacterial reverse mutation test, the in vitro chromosome aberration assay in human peripheral blood lymphocytes or in the in vivo mouse bone marrow micronucleus assay.”

“No evidence of genotoxicity of samidorphan was found in the in vitro Ames bacterial reverse mutation test, the in vitro chromosome aberration assay in human peripheral blood lymphocytes or in the in vivo mouse bone marrow micronucleus assay.”

“SAM is also non-carcinogenic as it did not induce tumors in male and female rats administered SAM for up to 95 weeks at exposures which are approximately 32 and 237 times the MRHD based on AUC, respectively and did not induce tumors in rasH2 transgenic mice administered SAM for 6-months.”

“SAM is also non-carcinogenic as it did not induce tumors in male and female rats administered SAM for up to 95 weeks at exposures which are approximately 32 and 237 times the MRHD based on AUC, respectively and did not induce tumors in rasH2 transgenic mice administered SAM for 6-months.”

“In safety pharmacology studies, SAM and metabolite RDC-9986 were not significant hERG channel blockers (IC50 values of 28.19 and >280 µM, respectively).”