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

“Nirmatrelvir was negative for mutagenic or clastogenic activity in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the in vitro micronucleus assay using human lymphoblastoid TK6 cells, and the in vivo rat micronucleus assays.”

“No carcinogenicity studies have been performed. Considering that the duration of treatment is limited to 5 days, the absence of carcinogenicity studies is in-line with the recommendations of ICH S1A.”

“In the rabbit EFD study, lower fetal body weights (9% decrease) were observed at 1,000 mg/kg/day in the absence of significant maternal toxicity findings.”

“In a cardiovascular safety pharmacology study in cynomolgus monkeys, small transient effects such as increased systolic, diastolic, and mean blood pressure (BP), heart rate (HR) decreases, and associated RR, PR, and QT interval increases were observed following oral administration of 150 (75 BID) mg/kg/day nirmatrelvir.”

“Nirmatrelvir was negative for mutagenic or clastogenic activity in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the in vitro micronucleus assay using human lymphoblastoid TK6 cells, and the in vivo rat micronucleus assays.”

“Nirmatrelvir was negative for mutagenic or clastogenic activity in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the in vitro micronucleus assay using human lymphoblastoid TK6 cells, and the in vivo rat micronucleus assays.”

“Nirmatrelvir was negative for mutagenic or clastogenic activity in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the in vitro micronucleus assay using human lymphoblastoid TK6 cells, and the in vivo rat micronucleus assays.”

“No carcinogenicity studies have been performed. Considering that the duration of treatment is limited to 5 days, the absence of carcinogenicity studies is in-line with the recommendations of ICH S1A.”

“No carcinogenicity studies have been performed. Considering that the duration of treatment is limited to 5 days, the absence of carcinogenicity studies is in-line with the recommendations of ICH S1A.”

“From in vitro and ex vivo data (studies 200804.QHJ, 20LJ076 and 20J075), there was no clinically meaningful effect of PF-07321332 on hERG, isolated guinea pig heart or isolated rat aorta assays.”