US FDA investigating safety risk of CAR-T cancer therapies

[November 29, 2023]  By Pratik Jain

(Reuters) - The U.S. Food and Drug Administration (FDA) said on Tuesday it was investigating cancer therapies made by Gilead Sciences, Johnson & Johnson, Novartis and others over the risk of hospitalizations and death due to a serious safety issue.

The FDA said it had received reports of patients developing a type of T-cell blood cancer after being treated with genetically modified cells known as chimeric antigen receptor T-cell therapies or CAR-T.

The treatment generally involves extracting disease-fighting white blood cells known as T-cells from a patient, re-engineering them to attack cancer and infusing them back into the body.

Since 2017, six CAR-T cell therapies have been approved by the FDA and all are for the treatment of blood cancers, including lymphomas and some forms of leukemia.

Maksim Mamonkin, a CAR-T expert at Baylor College of Medicine's Center for Cell and Gene Therapy, who oversees production of CAR-T treatments, said in clinical trials, secondary cancers are "definitely not something that we routinely see or something that we expect."

"Obviously, when you start treating thousands of patients with commercial products, that may become an issue just by chance."

Mamonkin said T-cell cancers can occur after patients receive other cancer treatments such as chemotherapy. If pre-cancerous cells were inadvertently collected and used to make CAR-T treatments, that could result in secondary cancers.

Dr. Julie Gralow, chief medical officer of the American Society of Clinical Oncology, said, “Based on the available data, the risk of T-cell malignancies due to CAR-T cell therapy appears to be low."

While such cancers have occurred in people who have received CAR-T therapy, she said the causal relationship — whether by chance or caused by the therapy — needs to be investigated.

Approved cancer therapies in this class include Bristol Myers Squibb's Breyanzi and its partnered therapy, Abecma, with 2seventy bio.

Signage is seen outside of the Food and Drug Administration (FDA) headquarters in White Oak, Maryland, U.S., August 29, 2020. REUTERS/Andrew Kelly/File Photo

J&J unit Janssen and Legend Biotech's Carvykti, Novartis AG's Kymriah, and Gilead unit Kite's Tecartus and Yescarta are also a part of the investigation.

Shares of Gilead closed down 0.6% at $74.51 on Tuesday. Legend shares fell 2.6% to close at $59.99. Shares of Autolus Therapeutics declined 4.8% to end at $4.55.

RBC analysts in a note said the concerns could be higher for Novartis' Kymriah, and extremely rare for all the other marketed CAR-Ts.

However, Mamonkin said the higher number of cases involving Kymriah could be related to the fact that the treatment is more commonly used in older adults, who are more prone to cancer.

Novartis said in a statement that there is no evidence to date that would change its confidence in Kymriah’s benefit or risk profile and that it has not identified a causal relationship between Kymriah and secondary malignancies.

The company added that it is "fully committed to patient safety and will continue to work with the FDA."

Gilead said it had cooperated with the FDA on its request for an analysis of the company's data, adding there was no evidence that treatment with either of its two therapies had a causal role in the development of new malignancies.

"We are confident in the overall safety profile of both Tecartus and Yescarta," Gilead told Reuters in an emailed statement.

J&J and Bristol Myers did not immediately respond to requests for comment.

(Reporting by Pratik Jain and Christy Santhosh in Bengaluru, and Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Krishna Chandra Eluri, Maju Samuel and Matthew Lewis)

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