Tecartus Labeling Update Causes Momentary Confusion in FDA Oversight of CAR-T Therapy Safety

In an unforeseen development, the FDA’s directive for a labeling alteration concerning Gilead Sciences’ Tecartus briefly vanished from the agency’s website. Contrary to initial assumptions, the FDA did not remove the CD19 CAR-T therapy from a broader safety alert. Instead, the regulatory body has opted to refine the language of a proposed boxed warning.

A revised missive of the FDA’s insistence that Gilead’s cell therapy unit, Kite Pharma, incorporate updated language addressing the risk of T-cell malignancies into Tecartus’ label. Unlike the original proposal encompassing other CAR-T therapies, the revised communication no longer explicitly mentions Tecartus patients experiencing T-cell malignancies.

The FDA’s delay in reposting the amended letter, following the removal of the original one dated January 19, led to a brief period of confusion. Notably, the FDA consistently communicates its determination that language concerning T-cell malignancies be included in the labeling for all BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies in letters to CAR-T manufacturers.

The adjustment in wording suggests that while the FDA still considers secondary T-cell cancers a classwide concern, Tecartus itself may not have witnessed such cases. Approved for treating mantle cell lymphoma and B-cell precursor acute lymphoblastic leukemia, Gilead’s CD19 CAR-T drug faces scrutiny for its safety profile.

A few months ago, the FDA initiated an investigation into the perceived “serious” risk of patients developing secondary T-cell malignancies post-commercial CAR-T therapy. Despite this, the agency has refrained from disclosing specific case numbers, associated products, or their characteristics since the investigation’s inception in November.

It remains unclear if the adjustment to the Tecartus letter is an isolated incident or if other letters require similar modifications.

Apart from Tecartus, several other CAR-T therapies, including Gilead’s Yescarta, Bristol Myers Squibb’s Breyanzi and Abecma, Johnson & Johnson and Legend Biotech’s Carvykti, and Novartis’ Kymriah, face FDA directives to include the safety warning in their labels.

Responding to the FDA’s communication, Novartis and J&J committed to updating the prescribing information for their respective CAR-T cell therapies to incorporate the risk of T-cell malignancies. Novartis, while experiencing a 1% drop in shares, reiterated its confidence in Kymriah’s safety profile, stating it has not identified a causal link with secondary T-cell malignancies.

The FDA’s revelation in November, reporting cases of patients developing T-cell blood cancer post-CAR-T therapy, has triggered increased scrutiny. Analysts anticipate these safety warnings may not dent the demand for cancer therapies, but they could raise questions about the technology’s suitability for treating immunity-related diseases. Gilead has pledged to collaborate with the FDA on the labeling request, asserting that their analysis has found no evidence establishing a causal role for Yescarta or Tecartus in the observed malignancies.

As the FDA asserts the applicability of T-cell malignancy risks to all therapies in the category, pharmaceutical companies, including Bristol Myers, are evaluating their next steps regarding the labels for Abecma and Breyanzi. Bristol Myers emphasized that it has not identified a causal relationship between its therapies and malignancies, with no reported cases in over 5 thousand treated patients.

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