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

“Solriamfetol was non-genotoxic in an adequate battery of genotoxicity assays.”

“Solriamfetol was not carcinogenic and did not induce tumors in rats or mice when administered orally at doses up to approximately 3.5- and 9- times the MRHD of 300 mg/day to rats and mice, respectively, based on AUC.”

“In embryo-fetal developmental studies, oral administration of solriamfetol during organogenesis caused maternal and fetal toxicities in rats and rabbits at doses ≥ 2- and 2.5- times- and was teratogenic at doses 9.5- and ≥ 2.5- times, respectively, the MRHD”

“The safety pharmacology of solriamfetol was evaluated in the cardiovascular, respiratory, and CNS systems. No severe adverse effects were identified at the clinically relevant doses.”

“Solriamfetol plate was not mutagenic in any of the tester strains in the presence or absence of metabolic activation.”

“Solriamfetol was not clastogenic in a valid in vitro mammalian cell chromosome aberration assay.”

“Solriamfetol, when orally administered at doses up to 250 mg/kg, was negative in a valid in vivo mouse micronucleus study.”

“Long-term oral carcinogenicity studies have been performed in mice, treated with daily solriamfetol doses of 20, 65 and 200 mg/kg for up to 104 weeks, and in rats, treated with daily solriamfetol doses of 35, 80 and 200 mg/kg for up to 101 weeks.”

“The executive carcinogenicity assessment committee concluded that these studies were adequate and that there were no drug-related neoplasms in either study.”

“Solriamfetol at concentrations of 0.1, 1, and 10 µM only induced 5%, 13%, and 19% inhibition of the hERG current, whereas the positive control astemizole induced 93% inhibition of hERG current at 10 nM.”