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

“Studies evaluating genotoxicity of biotechnology products, are not mandatory in accordance with ICH S6 guideline”

“On March 19, 2014, the applicant was informed that a carcinogenicity assessment of lecanemab would not be necessary based on the development of neutralizing anti-drug antibodies in rodents treated with lecanemab or the mouse surrogate, mAb158.”

“No reproductive and developmental toxicology studies were conducted with lecanemab. The sponsor was informed on November 6, 2012, that reproductive and development toxicology studies are not required”

“In accordance with ICH guidelines S6(R1) and S7A no stand-alone safety pharmacology studies were performed.”

“Genetic toxicology studies were not conducted because monoclonal antibodies are not expected to interact directly with DNA.”

“Genetic toxicology studies were not conducted because monoclonal antibodies are not expected to interact directly with DNA.”

“Genetic toxicology studies were not conducted because monoclonal antibodies are not expected to interact directly with DNA.”

“Carcinogenicity studies were not conducted because of the lack of pharmacological activity in rodent species (mouse, rat), making standard carcinogenicity studies infeasible.”

“On March 19, 2014, the applicant was informed that a carcinogenicity assessment of lecanemab would not be necessary based on the development of neutralizing anti-drug antibodies in rodents treated with lecanemab or the mouse surrogate, mAb158.”

“The core battery of safety pharmacology assessments was conducted in the 4-week pivotal study conducted in monkey. There were no adverse effects on cardiovascular, respiratory, or CNS function.”