Luxturna: what was done before first-in-human, and what came after?

“Because the pharmacology data indicated that efficacy could be achieved over a broad dose range, the determination of the optimal therapeutic dose also relied on safety data.”

“Scheduled Sacrifice Time Points Days 190 (two animals) and 217 (two animals)”

“In these studies, virus was injected subretinally either once only, or once into each eye, and twice into the same eye.”

“Animal reproductive studies have not been conducted with LUXTURNA.”

“The presence of AAV2-hRPE65v2 was not detected by qPCR in the gonads of healthy NHPs following subretinal administration.”

“studies to evaluate safety pharmacology, developmental and reproductive toxicity, genotoxicity, and carcinogenicity/tumorigenicity were not conducted or required for AAV2-hRPE65v2.”

“No animal studies have been conducted to evaluate the effects of LUXTURNA on carcinogenesis, mutagenesis, and impairment of fertility.”

“Thus, the risk for AAV vector-induced insertional mutagenesis/carcinogenesis, particularly in post-mitotic cells such as retinal cells, is considered low.”

“CHMP also advised that in vivo testing in 2-year carcinogenicity studies in mice or rats would not contribute meaningful data to assessing the risk of carcinogenicity.”