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

“Therefore, the carcinogenicity potential for pegaptanib sodium is considered low, based on the negative in vitro and in vivo genotoxicity assays for pegaptanib sodium and its component modified nucleotides.”

“The main argument considered by the CHMP in order to accept the lack of carcinogenicity studies was due to the very low systemic exposure obtained in the clinical population together with the apparent difficulty to perform relevant study obtaining both high systemic and intraocular exposure.”

“The reproductive toxicology program included range-finding embryo-foetal development studies in rabbit and mouse and a final embryo-foetal development study in the mouse.”

“Pegaptanib sodium was evaluated in animal models for cardiovascular, respiratory and neurobehavioral effects, at IV administered doses with associated systemic exposures up to 10-fold”

“In a battery of genotoxicity assays, 2’-FU and 2’-FC were negative in the Salmonella strains of the Ames assay, the SHE cell and the micronucleus assay but produced a small increase in revertant frequency with no relationship to dose in a single bacterial mutagenicity tester strain (E. coli).”

“In a battery of genotoxicity assays, 2’-FU and 2’-FC were negative in the Salmonella strains of the Ames assay, the SHE cell and the micronucleus assay but produced a small increase in revertant frequency with no relationship to dose in a single bacterial mutagenicity tester strain (E. coli).”

“In a battery of genotoxicity assays, 2’-FU and 2’-FC were negative in the Salmonella strains of the Ames assay, the SHE cell and the micronucleus assay but produced a small increase in revertant frequency with no relationship to dose in a single bacterial mutagenicity tester strain (E. coli).”

“The main argument considered by the CHMP in order to accept the lack of carcinogenicity studies was due to the very low systemic exposure obtained in the clinical population together with the apparent difficulty to perform relevant study obtaining both high systemic and intraocular exposure.”

“The main argument considered by the CHMP in order to accept the lack of carcinogenicity studies was due to the very low systemic exposure obtained in the clinical population together with the apparent difficulty to perform relevant study obtaining both high systemic and intraocular exposure.”

“above the exposures observed after a 3 mg/eye clinical dose. All studies were claimed to be performed according to GLP. Pegaptanib did not affect these parameters”