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

“The supporting clinical data from the predecessor product that used a similar vector (AAV5) as HEMGENIX was used to inform dosing for later clinical studies, and assessments of vector viral kinetics.”

“No repeated dose toxicity studies were conducted. This is acceptable, as only a single etranacogene dezaparvovec administration is intended in patients”

“The single IV dose toxicology studies and the analysis of the safety parameters were performed under GLP compliance.”

“The risk of germline transmission of the HEMGENIX predecessor was evaluated in healthy male mice administered 2.3x1014 gc/kg and mated with healthy naïve female mice on Day 6 post-dose.”

“However, there were no adverse effects on mating rates or fertility indices.”

“As haemophilia B is almost exclusively limited to male patients, and as the current MAA only comprises adult patients, dedicated EFD and PPND studies are not required.”

“Dedicated studies on carcinogenicity were not conducted with AMT-061 (nor AMT-060).”

“A low level of integrated vector DNA was distributed throughout the host genome with no predilection to specific integration sites, including in genes associated with malignant transformation in humans.”

“Studies to evaluate the carcinogenicity/tumorigenicity of HEMGENIX were not conducted. These studies are not warranted based on the nonclinical safety profile.”