FDA Adds Warning to J&J's Carvykti Label for Potentially Fatal Intestinal Disorder

The U.S. Food and Drug Administration (FDA) has updated the label of Johnson & Johnson (J&J) and Legend Biotech's multiple myeloma treatment, Carvykti, with a boxed warning for a potentially fatal intestinal inflammatory disorder. This development marks a significant safety update for one of the leading CAR-T cell therapies in the market.

New Boxed Warning for Immune Effector Cell-Associated Enterocolitis

The FDA's boxed warning addresses the risk of immune effector cell-associated enterocolitis (IEC-EC), a condition that has been observed in patients treated with Carvykti. This intestinal inflammatory disorder can develop within weeks or months after CAR-T cell infusion, presenting symptoms such as diarrhea, abdominal pain, and weight loss. In severe cases, IEC-EC can lead to gut perforation and sepsis, potentially resulting in fatal outcomes.

The warning is based on reports from clinical trials and post-marketing adverse event data. Patients who have developed IEC-EC have been treated with immunosuppressive therapies, including corticosteroids, and have required nutritional bloodstream infusions to bypass the digestive system.

Despite this new warning, the FDA maintains that the benefits of Carvykti continue to outweigh its potential risks. A J&J spokesperson reported that IEC-EC has occurred in approximately 1% of patients who have received Carvykti, based on a retrospective analysis of clinical trial data.

Carvykti's Market Position and Clinical Benefits

Carvykti, approved by the FDA in 2022, has quickly risen to become the world's top-selling CAR-T therapy. In the first half of this year, the drug generated sales of $808 million, surpassing Gilead's Yescarta, which held the title of first CAR-T blockbuster in 2022.

The treatment has demonstrated significant clinical benefits, including a 45% reduction in the risk of death compared to standard therapies in patients who have received one to three prior lines of treatment. This data is based on nearly three years of follow-up studies.

J&J reports that more than 8,500 patients have been treated with Carvykti to date. The drug's use was expanded to earlier treatment lines last year, allowing its administration as early as the second-line setting for multiple myeloma patients.

Broader Implications for CAR-T Therapies

This labeling update for Carvykti comes in the context of ongoing safety monitoring for all CAR-T cell therapies. Last year, the FDA added a boxed warning to all CAR-T treatments for the risk of secondary T-cell cancers. Other CAR-T products on the market include Novartis' Kymriah, Bristol Myers Squibb's Breyanzi and Abecma, and Gilead's Tecartus and Yescarta.

In a move to increase access to these innovative therapies, the FDA removed its Risk Evaluation and Mitigation Strategies (REMS) requirements for CAR-T blood cancer drugs four months ago. This change eliminated the need for hospitals and clinics to obtain special certification to administer CAR-T therapies, potentially broadening their availability to patients.

As the landscape of CAR-T therapies continues to evolve, the pharmaceutical industry and regulatory bodies remain vigilant in monitoring and addressing potential safety concerns while working to expand access to these groundbreaking treatments for cancer patients.