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

“A first-in-human, two-part, nonrandomized, open-label, multicenter, dosing finding Phase 1 study to evaluate the safety, efficacy, cellular kinetics/pharmacokinetics of a single dose of ABECMA in subjects with relapsed/refractory multiple myeloma (RRMM) (Study No. CRB-401, supportive study).”

“expression which represents the human equivalent dose (HED) of 2.05 x 108 CAR+ T cells for a 100-kg human.”

“No single or repeat-dose toxicity studies were conducted with ide-cel as traditional animal studies employing common toxicology study designs are not appropriate for ide-cel since autologous human T cells do not graft in immunocompetent animals.”

“No single or repeat-dose toxicity studies were conducted with ide-cel as traditional animal studies employing common toxicology study designs are not appropriate for ide-cel”

“No animal reproductive and developmental toxicity studies were conducted for bb2121 which is acceptable based on the product characteristics.”

“No animal reproductive and developmental toxicity studies were conducted for bb2121 which is acceptable based on the product characteristics.”

“No animal reproductive and developmental toxicity studies were conducted for bb2121 which is acceptable based on the product characteristics.”

“No carcinogenicity or tumorigenicity studies were conducted for bb2121. However, the applicant evaluated IL-2 independent growth in Study #10.”

“Additionally, an IL-2-independent growth assay of ABECMA® generated from five patient donors and two healthy donors showed no signs of uncontrolled cellular proliferation.”

“Conventional animal studies employing common toxicology study designs are not appropriate for ide-cel since autologous human T cells do not graft in immunocompetent animals and thus, in vivo nonclinical general safety, genotoxicity, carcinogenicity, developmental safety or reproductive safety studies were not conducted.”