Shares of Chimeric Antigen Receptor (CAR) T cell therapy companies plummeted on November 28, 2023, following an announcement from the U.S. FDA regarding an investigation into reports of patients developing cancer as a potential side effect of their treatments. The FDA’s notice highlighted that both clinical trials and post-market surveillance have yielded reports of T-cell malignancies, including CAR-positive lymphoma, in patients treated with BCMA- or CD19-directed autologous CAR T cell immunotherapies.
According to the FDA, there have been 19 reported cases of T-cell lymphoma associated with CAR-T treatments. A report from FiercePharma, based on data from investor William Blair, outlines the distribution of these adverse event reports across currently available CAR-T products.
Summary of FDA Adverse Event Reporting System (FAERS) Data for CAR-T Therapies:
| Therapy | Company | Indications | Total Reported Cases | Serious Cases | Deaths Reported | T-cell Lymphoma Cases Reported |
|---|---|---|---|---|---|---|
| Kymriah | Novartis (NYSE: NVS) | LBCL, FL, and ALL | 2,470 | 2,303 | 662 | 7 |
| Yescarta | Gilead (NASDAQ: GILD) | LBCL and FL | 3,729 | 3,551 | 746 | 3 |
| Carvykti | Legend Bio (NASDAQ: LEGN) / J&J (NYSE: JNJ) | MM | 408 | 251 | 28 | 1 |
| Breyanzi | BMS (NYSE: BMY) | LBCL | 202 | 172 | 38 | 1 |
| Abecma | BMS (NYSE: BMY) | MM | 528 | 454 | 60 | 0 |
| Tecartus | Gilead(NASDAQ: GILD) | MCL and ALL | 609 | 570 | 136 | 0 |
LBCL: Large B-cell lymphoma; FL: Follicular lymphoma; ALL: Acute lymphoblastic leukemia; MM: Multiple myeloma; MCL: Mantle cell lymphoma.
The FDA emphasized that the overall benefits of these therapies continue to outweigh the potential risks for their approved indications, while the investigation aims to determine whether additional regulatory measures are necessary. CAR-T therapies are typically administered to patients who have exhausted all other treatment options and are facing imminent mortality.
Novartis reported that over 10,000 patients have been treated with the CD19-targeted Kymriah, with no causal link identified between the drug and secondary malignancies. Gilead echoed this sentiment, noting that its CD19-targeted therapies, Tecartus and Yescarta, have been given to a cumulative total of 17,700 patients. Legend Biotech, whose Carvykti has been administered to 2,000 patients, pointed out that multiple myeloma patients are at risk for T-cell malignancies even without CAR-T treatment, with an incidence rate of 0-554 per 100,000 patients. Furthermore, other myeloma therapies have been associated with an increased risk of secondary malignancies.
The announcement resulted in a decline in share prices for companies developing CAR-T therapies, reflecting investor concerns over the implications of the FDA’s findings.- Flcube.com
