Focus On Bristol Myers, Gilead Sciences, Johnson & Johnson, Novartis: FDA To Issue Classwide Black Box Warning on CAR-T Therapies For Blood Cancer Treatment

In a significant development, the FDA is set to impose a classwide black box warning following its investigation into secondary T-cell cancers arising from the use of existing CAR-T therapies. 

In its January 19 notification letters, the agency stressed that the potential risk applies to all currently approved CAR-T products. 

The regulatory body has mandated label updates for all six commercial CAR-T therapies, including those of major players such as Bristol Myers Squibb & Co BMY, Gilead Sciences Inc’s Kite Pharma GILD, Johnson & Johnson JNJ, and Novartis AG NVS. This move places T-cell malignancies in the boxed warning section, the most severe safety alert on a medication’s label.

The affected products include Bristol’s Abecma and Breyanzi, Kite’s Yescarta and Tecartus, J&J’s Carvykti (developed in partnership with Legend Biotech Corporation LEGN), and Novartis’ Kymriah. 

These therapies are individually approved for multiple myeloma, large B-cell lymphoma, and other blood cancers. 

The FDA specifically instructs the companies to include a paragraph in the boxed warnings indicating, “T cell malignancies may occur following treatment with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including,” followed by the product’s name. 

This directive follows the FDA’s investigation into secondary T-cell malignancies, marked as “serious,” among patients receiving BCMA- or CD19-targeted CAR-Ts. 

In November, the FDA said it received reports of patients developing T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T cell immunotherapies.

The agency said it’s weighing “the need for regulatory action” in response to clinical testing and safety monitoring reports tied to commercial use. 

The identified risk applies to all approved CAR-T therapies, although the agency noted that “the overall benefits of these products continue to outweigh their potential risks for their approved uses.

In December, another big pharma, AstraZeneca Plc AZN, agreed to acquire Gracell Biotechnologies Inc GRCL, further strengthening AstraZeneca’s cell therapy portfolio, for $2/share.

The proposed acquisition will enrich AstraZeneca’s growing pipeline of cell therapies with GC012F, a clinical-stage FasTCAR-enabled BCMA, and CD19 dual-targeting autologous chimeric antigen receptor T-cell (CAR-T) therapy, a potential treatment for multiple myeloma, as well as other hematologic malignancies and autoimmune diseases including systemic lupus erythematosus.

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