The FDA is investigating safety risks in patients receiving CAR T-cell immunotherapies after reports of T-cell malignancies, including CAR-positive lymphoma. All six approved CAR T drugs are being placed under increased scrutiny by the American regulators. We spoke with Jamal El-Mosleh, CEO of cell- and gene therapy company Elicera Therapeutics, to see how this might affect a CAR T developer like Elicera.
The 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 revolutionised the oncology area the past decade. The treatment genetically reprograms a patient’s T cells, a key part of the immune system, to recognise and attack cancer cells.
Six CAR T drugs have been approved by the FDA since 2017: Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta. These have mainly been used to treat blood cancers, such as leukaemia, lymphoma, and myeloma, and, so far, they have been quite successful. Physicians have reported dramatic improvements and even curing many patients who were not responding well to more traditional treatments, like chemotherapy, radiation, and surgery.
Read more about the promise of CAR T therapies here.
FDA investigates “serious risk” of CAR T therapies
However, on November 28, the FDA announced that it is investigating a “serious risk” of patients developing new cancers after treatment with these therapies. According to the FDA, the probe is based on reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed CAR T cell immunotherapies.
While some patients involved have had to be hospitalised or have even died, the agency itself says that the overall benefits of these products continue to outweigh their potential risks.
Are CAR T developers affected?
In Sweden, the only company working with CAR T technology is Elicera Therapeutics. 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 targets as the ones currently on the market.
ELC-301 is entering the clinic early in 2024 for the treatment of B-cell lymphoma, and targets CD20. Meanwhile, ELC-401, in preclinical development for the treatment of glioblastoma, a solid tumour, targets the IL13Ra2 receptor.
Elicera’s stock price has been unaffected by the FDA’s announcement. In fact, since late September, the share price has shot up 100 per cent.
A talk with Elicera’s CEO
To better understand the downstream effects of the FDA’s increased scrutiny towards currently-commercialised CAR T therapies, BioStock spoke with Elicera’s CEO Jamal El-Mosleh.
Jamal, the FDA have received reports of new cancer arising from marketed CAR T-cell treatments. Was it known that this could be a potential issue?
– Yes, the risk of T-cell malignancies has been known. We have to remember that patients that are eligible for approved CAR T-treatments are in very poor condition with no other treatment alternatives and actually stand a relatively good chance to be cured. As the FDA has also concluded, so far, the benefits of CAR T-cell therapies continue to outweigh the potential risks. It may also be worth mentioning that the reported risk of secondary cancer is 2-5 per cent for patients treated with chemotherapy, which is similar to what has been seen in patients treated with gene-modified cells such as CAR T-cells. However, we need to closely monitor these patients to see what is happening.
What might be the cause of the issue?
– It’s been proposed that since the CAR gene is inserted randomly into the T-cell genome, which might disturb gene expression, or the genome stability, this in turn could result in the development of cancer.
Do current CAR T developers need to revisit their development strategies because of this?
– No, we don’t think so. I mean, we need to see the outcome of FDA’s investigation first of course, but personally I’m not expecting CAR T developers to have to change their development strategies. We will monitor patients after CAR-T therapy for at least 15 years to follow-up also on any potential secondary malignancies.
How do Elicera’s candidates differ from those currently on the market?
– Elicera’s candidates are differentiated through our iTANK-platform, a universal CAR T-arming technology that elicits a parallel immune response against multiple targets on tumours cells and counteracts the immunosuppressive tumour microenvironment in solid tumours. Our upcoming clinical study, CARMA, in B-cell lymphoma will be done with an iTANK-armed CAR T-cell therapy targeting CD20, in contrast to CD19 that the other three approved CAR T-therapies are targeting. Since 50% of patients are expected to relapse and lose the target antigen, we think ELC-301 stands a good chance to meet this unmet medical need.
Does the hightened 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 only quite recently became a public company and I think the company is still relatively unknown in the investment community. We have spent significant time and resources in “marketing” Elicera, and I think our growing base of shareholders has been reflected in the share price.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.