Idecabtagene vicleucel

Idecabtagene vicleucel is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of idecabtagene vicleucel results in CAR-positive T cell proliferation, cytokine secretion and subsequent cytolytic killing of BCMA-expressing cells.

Following idecabtagene vicleucel infusion, the CAR-positive T cells proliferate and undergo rapid multi-log expansion followed by a bi-exponential decline. The median time of maximal expansion in peripheral blood (T_max) occurred 11 days after infusion.

Idecabtagene vicleucel can persist in peripheral blood for up to 1 year post-infusion.

Idecabtagene vicleucel transgene levels were positively associated with objective tumour response (partial response or better). The median C_max levels in responders (N=93) were approximately 4.5-fold higher compared to the corresponding levels in non-responders (N=34). Median AUC0-28days in responding patients (N=93) was approximately 5.5-fold higher than non-responders (N=32).

Special populations

Renal and hepatic impairment

Hepatic and renal impairment studies of idecabtagene vicleucel were not conducted.

Effects of age, weight, gender or race

Age (range: 33 to 78 years) had no impact on idecabtagene vicleucel expansion parameters. The pharmacokinetics of idecabtagene vicleucel in patients less than 18 years of age have not been evaluated.

Patients with lower body weight had higher cellular expansion. Due to high variability in pharmacokinetic cellular expansion, the overall effect of weight on the expanison parameters of idecabtagene vicleucel is considered not to be clinically relevant.

Gender had no impact on idecabtagene vicleucel expansion parameters.

Race and ethnicity had no significant impact on idecabtagene vicleucel expansion parameters.

Idecabtagene vicleucel comprises engineered human T cells, therefore there are no representative in vitro assays, ex vivo models, or in vivo models that can accurately address the toxicological characteristics of the human product. Hence, traditional toxicology studies used for drug development were not performed. Genotoxicity assays and carcinogenicity studies were not conducted.

In vitro expansion studies from healthy donors and patients showed no evidence for transformation and/or immortalisation and no preferential integration near genes of concern in idecabtagene vicleucel T cells.

Given the nature of the product, non-clinical studies on fertility, reproduction and development were not conducted.