Slow-and-Steady Is the Right Approach for Evaluating Cell Therapy for Autoimmune Diseases

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Peter A. Merkel, MD, MPH, the chief of the Division of Rheumatology and a professor of medicine and professor of epidemiology at Penn Medicine, discussed clinical trial design considerations for this emerging field.

Peter A. Merkel, MD, MPH, the chief of the Division of Rheumatology and a professor of medicine and professor of epidemiology at Penn Medicine

Peter A. Merkel, MD, MPH
Credit: Penn Medicine

2023 saw a rapid increase in interest in investigating engineered cell therapy modalities, which have previously proved their worth in oncology, for the potential treatment of autoimmune disease. This involved a number of companies launching clinical trials for chimeric antigen receptor T-cell (CAR-T) therapies in lupus and other autoimmune diseases, with some companies even launching multiple trials in 2023 for different autoimmune disease indications.

In light of this spike in interest, the first Cell Therapy for Autoimmune Disease Summit was held from November 28-30, 2023, in Philadelphia, Pennsylvania, to bring together interested parties to discuss the best paths forward. Notably, Peter A. Merkel, MD, MPH, the chief of the Division of Rheumatology and a professor of medicine and professor of epidemiology at Penn Medicine, spoke at a panel discussion at the conference called “Improving Clinical Endpoints & Optimizing Trial Design”. After the session, CGTLive® sat down with Merkel to learn more about what was discussed in the session, including his views on how the clinical community should approach trials in this field.

CGTLive: Can you give some background info about the panel you participated in?

Peter A. Merkel, MD, MPH: There is incredible enthusiasm in the field of rheumatology and in other autoimmune areas for the potential for CAR-T and other cell therapies as therapeutic intervention for these often very difficult diseases. The data from Germany—but also data now from China and other places—are very encouraging for lupus nephritis, as well as other autoimmune diseases: rheumatic, neurologic, and others. There's been tremendous interest by the investigator community and patients, but also by companies. There's now a large number of companies interested in conducting and planning to conduct clinical trials in a variety of autoimmune diseases, using a variety of modalities from CD19 CAR-T, to T-regulatory cells, to other approaches. This session that I was a panelist on was set up to discuss some of the opportunities and challenges with conducting clinical trials in nononcologic autoimmune diseases.

What were the main ideas discussed during the session?

The main points covered how to think about balancing the benefits and the risks of a new therapy in patients with autoimmune disease. I think we focused on the tremendous unmet need for a variety of diseases ranging from lupus—especially lupus nephritis, but other parts of lupus—to scleroderma, to vasculitis, to myositis, to myasthenia gravis, and multiple sclerosis and other neurological diseases and dermatologic diseases as well because within these diseases there are often subgroups of patients who have tremendous unmet need that we're just not treating effectively for serious manifestations. There's a lot of interest in looking at cell-based therapy, especially B-cell depleting therapies. That being said, there are risks—for the preparatory therapy required, [and there is] the long-term risk or unknown of this immunomodulation, especially in these new diseases. How do you balance those risks experimentally and with patience? I think we all agree that a careful approach to doing experiments is appropriate given the promise of preliminary data, as is going at a slow pace to make sure we're doing this safely, especially by choosing patients that are sort of—how would you put it?—sick, but not too sick and making sure that we're showing benefit and pausing regularly to make sure we're doing this in a safe manner.

We also discussed clinical trial design challenges. These aren't going to be trials of hundreds of patients with randomized groups. What is enough therapy? What is enough data to warrant an understanding that a drug or a product is effective or not effective? Is it enough evidence that the FDA and other regulatory agencies around the world will approve that therapy? And those are not clear; this is a new space. How much information do you need? How do you know when to go on to the next thing? We need to figure that out as a community of investigators and companies and regulators and patients, and I think we will.

What are the big-picture implications that the healthcare community should take away from this?

I think the big picture implications are that if the early excitement and promise is real and comes true—even somewhat—that there's opportunity here perhaps to be transformative in the therapy for some patients with some autoimmune diseases. It is unlikely this will be appropriate for all different autoimmune diseases—or different approaches will be needed for different diseases—or there'll be subsets of patients where it works and doesn't work.

This probably needs to work moderately to extremely well for it to be worth it economically and from a risk-benefit standpoint. But I think there are real opportunities here to take our treatments to another level to help our patients. But caution is appropriate. The number of patients treated to date are few. We need to be careful, do this safely, and be self-critical as we go forward. These are a series of experiments.

This transcript has been edited for clarity.

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