3 progressive MS patients see lower disability with CAR T-cell therapy
Gains in walking, hand function seen, along with oligoclonal band resolution
A CAR T-cell therapy from Iaso Biotherapeutics was tolerated well and led to marked improvements in disability for three people with progressive forms of multiple sclerosis (MS), according to early data from a Phase 1 clinical trial.
After a single dose of equecabtagene autoleucel, patients saw rapid and sustained benefits, the company announced. These included improved walking and hand function, along with the disappearance of oligoclonal bands, which are markers of inflammation in the spinal fluid associated with MS.
The findings were shared at the 11th Congress of the European Academy of Neurology (EAN) in the presentation “Anti-BCMA CAR T cell therapy in patients with multiple sclerosis.”
Equecabtagene autoleucel is an autologous CAR T-cell therapy, meaning it’s made from a person’s own T-cells, which are collected from a patient and modified to carry a chimeric antigen receptor (CAR), a man-made receptor that enables the cells to target and destroy specific cells once they’re infused back into the body.
The T-cells in equecabtagene autoleucel are equipped to target BCMA, a protein on the surface of B-cells, which are immune cells that play an important role in MS. By targeting BCMA, the therapy depletes the body’s B-cells to reduce the inflammatory processes that drive MS.
Results of CARTinNS study
Equecabtagene autoleucel is approved in China as Focaso for multiple myeloma, a cancer of B-cells.
Researchers at Tongji Hospital in China are sponsoring a Phase 1 clinical trial called CARTinNS (NCT04561557) to evaluate equecabtagene autoleucel in people with MS and other autoimmune diseases that affect the nervous system. All the participants in the Phase 1 study will be treated with a single infusion at varying doses, the main goal being to evaluate its safety.
The EAN presentation covered data from three participants in CARTinNS who had progressive forms of MS, two women with secondary progressive MS (SPMS) and a man with primary progressive disease (PPMS). All three had been previously treated with several approved MS therapies. [see table 1]
Before equecabtagene autoleucel treatment, the two SPMS patients had an Expanded Disability Status Scale (EDSS) score of 6, meaning they needed an aid to walk even short distances. After three months, the EDSS scores in both decreased — to 5.5 in one patient and 5 in the other — meaning they could walk short distances without an aid. The man with PPMS also saw an EDSS reduction — from 7 at the trial’s start, meaning he needed a wheelchair to get around, to 5.5 after three months.
Other measures of arm and hand dexterity, and walking function also improved over time in all three patients, and there were no new or enlarged lesions. All three were also negative for oligoclonal bands, which are indicators of B-cell-driven inflammation in the brain and spinal cord.
The researchers said equecabtagene autoleucel shows “high efficacy in treating progressive MS, as demonstrated by improved physical function and resolution of [oligoclonal bands].”
The therapy was generally well tolerated. Serious cases of low immune cell counts (neutropenia and lymphopenia) were observed only within the first month after treatment.
CAR T-cell therapies can cause a potentially life-threatening inflammatory reaction called cytokine release syndrome. All three patients experienced this, but it was mild and transient in all, and no issues related to neurological toxicity were observed.
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