American Food and Drug Administration (FDA) announced last week that it is investigating reports of secondary cancers in patients who have received CAR T-cell therapy. This type of immunotherapy has revolutionized the field of oncology over the past decade. The treatment reprograms a patient's T cells, a key part of the immune system, to recognize and attack cancer cells.
Since 2017, six CAR T drugs have been approved by the FDA: Abecma, Breyanzi, Carvykti, Kymriah, Tecartus and YescartaThese have been used primarily to treat blood cancers, such as leukemia, lymphoma, and myeloma, and so far they have been quite successful. Doctors have reported dramatic improvements in patients, and even cases of curing patients, who did not respond well to more traditional treatments, such as chemotherapy, radiation, and surgery.
Learn more about CAR T therapies here.
FDA investigates “serious risk” with CAR T therapies
However, on November 28, the FDA announced that it is investigating a “serious risk” for patients to develop new cancers after treatment with these therapies. According to the FDA, the review is based on reports of T-cell malignancies, including CAR-positive lymphoma, in patients treated with BCMA- or CD19-targeted CAR T-cell immunotherapies.
Although some of the patients in question have had to be hospitalized or even died, the agency itself says that the overall benefits of these products may outweigh the potential risks.
Are CAR T developers affected?
In Sweden, Elicera Therapeutics is the only company working with CAR T technology. The cell and gene therapy company has two CAR T projects in its pipeline, ELC-301 and ELC-401. Neither of these have the same goals as the CAR T treatments currently on the market.
ELC-301 will enter the clinic in early 2024 for the treatment of B-cell lymphoma and targets CD20. In parallel, preclinical development of ELC-401, which targets the IL13Ra2 receptor, is underway for the treatment of glioblastoma, a solid tumor.
Elicera's share price has not been affected by the FDA's announcement. In fact, since the end of September, the share price has risen by 100 percent.
A comment from Elicera's CEO
To better understand the effects of the FDA's increased scrutiny of the currently commercialized CAR T therapies, BioStock spoke with Elicera CEO Jamal El-Mosleh.
Jamal, the FDA has received reports of new cancers resulting from marketed CAR T-cell therapies. Was this known to be a potential problem?
– Yes, the risk of T-cell malignancies has been known. We must remember that patients eligible for approved CAR T therapies are in very poor condition, lack other treatment options, and actually have a relatively good chance of being cured. The FDA has also concluded that the benefits of CAR T-cell therapies to date continue to outweigh the potential risks. It may also be worth mentioning that the reported risk of secondary cancer is 2-5 percent for patients treated with chemotherapy, which is similar to what has been seen in patients treated with genetically modified cells such as CAR T cells. However, we need to closely monitor these patients to see what happens.
What could be the cause of the problem?
– It has been suggested that when the CAR gene is inserted randomly into the T-cell genome, this can disrupt gene expression, or genome stability, which in turn can lead to the development of cancer.
Do CAR T developers need to revise their development strategies because of this?
– No, we don't think so. I mean, of course we have to see the results of the FDA investigation first, but personally I don't expect CAR T developers to have to change their development strategies. We will follow patients after CAR-T treatment for at least 15 years to follow up on any secondary malignancies.
How do Elicera's candidates differ from those on the market today?
– Elicera’s candidates are differentiated by our iTANK platform, a universal CAR T-arming technology that elicits a parallel immune response against multiple targets on tumor cells and counteracts the immunosuppressive tumor microenvironment in solid tumors. Our upcoming clinical trial, CARMA, in B-cell lymphoma will be conducted with an iTANK-armed CAR T-cell therapy targeting CD20, as opposed to CD19, which the other three approved CAR T therapies target. Since 50 percent of patients are expected to relapse and lose the target antigen, we believe ELC-301 has a good chance of addressing this unmet medical need.
Does the increased scrutiny from the FDA worry Elicera at all?
– At this point, not at all.
Finally, what explains Elicera's rise on the stock market since September?
– Elicera was listed quite recently and I believe the company is still relatively unknown in investment circles. We have invested a lot of time and resources into “marketing” Elicera and I believe our growing base of shareholders has been reflected in the share price.