The FDA investigation into secondary T-cell cancers following treatment with existing CAR-T therapies is poised to lead to a class wide black box warning. The FDA requires label updates to include T-cell malignancies in the boxed warning section of all CAR-T therapies. A black box warning is the most serious alert on a medication’s label.
J&J’s Legend Biotech-partnered Carvykti and Novartis’ Kymriah are among the products involved. Multiple myeloma, large B-cell lymphoma and other blood cancers are treated with the products. The boxed warnings should include a paragraph stating that T-cell malignancies may occur following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including. The same language is required in the warning section of a drug’s label.
Less than two months after the FDA launched an investigation into secondary T-cell malignancies among patients who received CAR-Ts, the required label update comes. The risk was labeled as serious by the agency because of cases it had received from clinical trials and postmarketing research. The potential risk was deemed applicable to all CAR-T products by the FDA from the beginning. Industry watchers believe that a classwide boxed warning is likely to come next.
The FDA has decided that the T-cell malignancy safety signal should be included in the labeling of all genetically modified autologous T cell immunotherapies. Even future CAR-T hopefuls that fit the description will be subject to a boxed warning. Gracell has a dual-targeting GC012F that is the centerpiece of the $1 billion acquisition of the Chinese biotech. The FDA distinguishes between autologous therapies and off-the-shelf CAR-T therapies.
The companies can either file a supplement with different wording or meet the FDA’s demand and submit it. A rebuttal statement detailing their disagreements can be submitted. The companies must submit a response within 30 days if they want to avoid enforcement action. J&J will work with the FDA to update the Carvykti prescription information. J&J is confident in the favorable benefit-risk profile of Carvykti with more than 2,000 patients having been treated.
A month ago, Carvykti was updated with a boxed warning about secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, following treatment with the BCMA CAR-T.
Fierce pharma was told by the company that it will update the label in accordance with FDA guidance. The Swiss pharma pointed to 10,000 patients that have received Kymriah worldwide, saying it has not found sufficient evidence to declare a causality between CD19 therapy and T-cell malignancies. The company that got the CAR-T therapies from its acquisition of Celgene said it hasn’t found a relationship between its products and T-cell cancer.
The company will determine appropriate next steps in the interest of patients and healthcare providers as it reviews FDA’s changes. The latest analysis of more than 15,500 patients treated with Yescarta and more than 2,700 patients treated with Tecartus didn’t establish a role for the drug in the development of T-cell malignancies, a spokesman said. The FDA is allowing the products to stay on the market because of their benefit-risk profiles.
In a commentary published in Nature Medicine a few days ago, several cell therapy experts, including CAR-T pioneers Bruce Levine, PhD, and Carl June, M.D., suggested that treatment centers should continue to use those commercial CAR-T products. The rate of T-cell malignancies observed is far lower than that seen with some other treatments. The FDA is currently reviewing J&J and Legend’s application for Carvykti as a second-line multiple myeloma therapy, and the agency will convene an advisory committee meeting to discuss Bristol’s bid to move AbeCMa into the third-line setting. Yescarta is being tested in patients with high-risk large B-cell lymphoma.
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https://www.fiercepharma.com/pharma/fda-wants-classwide-boxed-warning-all-commercial-car-t-therapies-amid-secondary-cancer
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