mRNA CAR T Cell Therapy Receives FDA’s Rare Pediatric Designation to Treat Juvenile Dermatomyositis

In September 2024, the U.S. Food & Drug Administration (FDA) granted its rare pediatric disease designation to Descartes-08 for the treatment of juvenile dermatomyositis.¹

The FDA grants the rare pediatric disease designation for serious and life-threatening diseases that principally affect children aged 18 years or younger and fewer than 200,000 people in the U.S. Juvenile dermatomyositis is a rare pediatric autoimmune disorder marked by skin rash and severe muscle inflammation affecting multiple organ systems, including the joints, heart, lungs, kidneys, eyes and gastrointestinal systems. The symptoms can range from mild to life-threatening and include fatigue, joint pain, muscle weakness and fever. The condition affects approximately two to four children per million, or about 4,000 children in the U.S.^1,2

Treatment

The drugs currently used to manage myositis are not FDA approved for the treatment of myositis and are being used off label. However, they are all approved for conditions similar to myositis. The use of these drugs for myositis is based on small clinical trials, expert experience and individual reports in the literature of effectiveness for myositis.² These treatments include systemic glucocorticoids, methotrexate and other immunosuppressive agents, and intravenous immunoglobulin (IVIG).

Descartes-08, an mRNA cell therapy, is an autologous mRNA-engineered chimeric antigen receptor T cell therapy (mRNA CAR T cell) targeting B cell maturation antigen (BCMA). The agent is designed to be administered without preconditioning chemotherapy and does not use integrating vectors, unlike other FDA approved CAR T cell therapies.³

CAR T-Cell Therapies

CAR T cells, a type of cell therapy, have become a powerful option in the oncologist’s toolbox and are gaining ground in rheumatology. But they are cost prohibitive. Current FDA-approved CAR T cell therapies are individually customized, with a treatment cost of more than $450,000 per dose.

In CAR T cell therapy, a patient’s own T cells are collected from their body and re-engineered in the lab to produce new surface proteins called CARs. Millions of these revamped T cells are manufactured and infused back into the patient, where the CARs bind to the target cells.

“CAR T cells are the equivalent of ‘giving patients a living drug,’” says Renier J. Brentjens, MD, PhD, Memorial Sloan Kettering Cancer Center in New York, an early leader in the CAR T cell field.³

Side effects from CAR T cell treatments include cytokine release syndrome, which can lead to very high fever, severe hypotension and sometimes fatalities.

“The number one cause of non-relapse mortality in most patients is infection,” says Matthew J. Frigault, MD, clinical director, Cellular Therapy Service, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, Boston. “That’s because oncology and rheumatology patients don’t have normal functional immune systems to begin with.”⁴

Not including juvenile dermatomyositis, seven CAR T cell therapies are FDA approved for lymphoma, some leukemias and multiple myeloma in both adults and children.

The benefits of these therapies need to be carefully weighed along with the risks.

More to Come

In January, Cartesian Therapeutics Inc. announced that it had received written FDA agreement under the Special Protocol Assessment process on the overall design of the company’s planned phase 3 AURORA trial for Descartes-08 for the treatment of adults with generalized myasthenia gravis.⁵ It is also in phase 2 clinical development for the treatment of adults with systematic lupus erythematosus. A clinical trial is planned for additional autoimmune diseases.

Researchers have also begun to rethink the source of immune cells for CAR T cell therapies—using T cells collected not from patients, but from healthy donors. The goal: The creation of off-the-shelf CAR T cell therapies that would be immediately available for use rather than having to be manufactured for each patient.³ 

Updated Feb. 12, 2025, with additional information about CAR T cells therapies and sidebar.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Cartesian Therapeutics receives FDA rare pediatric disease designation for descartes-08 for the treatment of juvenile dermatomyositis [news release]. Cartesian Therapeutics Inc. 2024 Sep 9.
2. Types of myositis: Juvenile myositis. The Myositis Association. 2024.
3. CAR-T cells: Engineering patients’ immune cells to treat their cancers. National Cancer Institute. 2022 Mar 10.
4. Shapiro SC. CAR-T cells: Are we closer to drug-free remission than we think? The Rheumatologist. 2024 Jul;18(7).
5. Cartesian Therapeutics announces FDA Special Protocol Assessment Agreement for phase 3 AURORA trial of descartes-08 in myasthenia gravis [news release]. Cartesian Therapeutics Inc. 2025 Jan 7.