Qalsody: what flexibility did regulators accept, and why?

“Due to the severity of the indication, the carcinogenic potential of tofersen is to be conducted post-approval.”

“In agreement with the CHMP (EMA/CHMP/SAWP/229464/2019) carcinogenicity studies with tofersen are regarded dispensable with respect to the life-threatening nature of ALS, the negative genotoxic potential and the absence of (pre)neoplastic changes, cell proliferation, and immune or endocrine dysfunction in chronic toxicity studies in mice and NHP’s.”

“Considering that tofersen is not pharmacologically active in mice and rabbits, these studies do not provide data regarding the pharmacological activity of tofersen in terms of its potential effects on reproduction or development. This limits the predictive value of these studies in terms of human safety.”

“A literature review of the available data on the effects of SOD1 down-regulation indicates that the potential effects of ASO (tofersen) on reproduction and development are likely to be low; however, they are currently unknown. The lack of pharmacologically relevant studies with regard to pregnancy and fertility is now also adequately reflected in sections 4.6 and 5.3 of the SmPC.”