Waltham, MA – A small study of 15 patients published Thursday in The New England Journal of Medicine provides strong evidence of the therapeutic potential of CD19 CAR-T therapies in autoimmune disorders.
The study, conducted in Germany, enrolled patients who had been diagnosed with systemic lupus erythematosus (SLE), idiopathic inflammatory myositis or systemic sclerosis. Study participants had severe and progressive disease and were resistant to at least two different immunomodulating agents. CAR-T therapies were offered through an expanded access program in Germany, meant for critically ill patients.
After a median follow-up of 15 months, all eight SLE patients achieved disease remission based on the Definition of Remission in SEL tool, a unified criteria to evaluate remission in SLE patients which factors in other indices and the need for treatments.
All four systemic sclerosis patients also saw reduced scores in the European Scleroderma Trials and Research Group activity index, indicating lower disease activity. In addition, all three patients with idiopathic inflammatory myositis demonstrated major clinical response, as evaluated by the American College of Rheumatology–European League against Rheumatism scale.
All patients ultimately were able to stop immunosuppressive treatment.
In terms of safety, 11 patients developed cytokine release syndrome, 10 of which were grade 1 while one was categorized as grade 2. One patient also developed grade 4 neutropenia, which was resolved after stopping sertraline, pregabalin and doxazosin treatment and following an injection of granulocyte colony-stimulating factor.
“The dynamics of CAR T-cell expansion and of B-cell ablation were highly consistent among patients” despite having different diseases and prior treatment exposures, the researchers wrote in their paper, noting that the side effects were also “minimal” with no “prolonged bone marrow toxic effects.”
“Given that patients had full B-cell reconstitution for up to two years without having relapses, it seems that a single injection of CD19 CAR T-cell therapy can lead to a long-lasting remission,” the researchers added.
CAR-T therapies make use of a patient’s own T cells—which have been genetically altered in a lab to express a specific receptor—to seek out a target. This approach has worked well for cancer as the FDA has approved six CAR-T therapies, which are extremely effective for specific leukemias and lymphomas.
In Thursday’s NEJM study, the researchers designed the CAR-T therapies to target CD19, a key surface protein found on B cells, which are what typically drive autoimmune diseases.
While harnessing CAR-T therapies for autoimmune diseases is a relatively new strategy, a handful of companies have already started working on this approach. These include Bristol Myers Squibb, which is developing its CD19 NEX-T program in SLE and multiple sclerosis, both of which are currently in Phase I.
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