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

“Activity was demonstrated in the dose range 1011-1013 gc/kg compared to the proposed human dose of 1x1012 gc/kg.”

“Repeated dose toxicity studies were not conducted as Glybera will be administered once at multiple sites intramuscularly.”

“The non-clinical toxicology programme of Glybera included one single dose toxicity study performed with AMT-010 with a 90-day observation period, two single dose toxicity studies performed with AMT-011 with a 180-day and 105-day observation period, respectively, and a combined reproductive toxicology and breeding study performed with AMT-011.”

“Reproductive toxicity was studied in pregnant mice in whom no effects of female reproduction or fetal development were detected.”

“Reproductive toxicity was studied in pregnant mice in whom no effects of female reproduction or fetal development were detected.”

“Carcinogenicity studies have not been conducted. The applicant argues that the studies conducted to assess integration are sufficient to address risk of carcinogenicity.”

“Studies using techniques to selectively digest genomic DNA showed that the majority (97%) of AMT-011 is not integrated into the genome, implying their presence episomally.”

“In vivo carcinogenicity studies have not been conducted. The applicant argued that there is no existing study design that would be accepted as relevant to assess insertional mutagenesis and the risk of oncogenicity”