AAN 2026 Mobility improvement with CAR T-cell therapy in stiff person syndrome

medwireNews: Mivocabtagene autoleucel (Miv-cel) chimeric antigen receptor (CAR) T-cell therapy given as a single dose may provide sustained symptom relief for patients with stiff person syndrome (SPS), shows a phase 2 trial.

The KYSA-8 study was presented at the AAN Annual Meeting in Chicago, Illinois, USA, by Amanda Piquet, from the University of Colorado Anschutz in Aurora, USA.

She explained that “Miv-cel is a unique fully human, autologous CD19 CAR-T therapy with a CD8 co-stimulation, designed for potency and tolerability.”

The presenter continued that “in this landmark, pivotal study in SPS, a single dose of Miv-cel resulted in significant, robust, rapid improvements in mobility, disability, stiffness and hypersensitivity,” and the data support an SPS Biologics License Application for Miv-cel.

As there are currently no US FDA approved therapies for SPS, Piquet believes that “Miv-cel addresses high, unmet need in this progressive disease.” 

A total of 26 adults (62% women; mean age 56 years) with SPS and an inadequate response to at least one immunomodulatory therapy participated in the trial. The patients were positive for high-titer GAD65 or GlyR antibodies at screening or previously. After discontinuing any SPS immunotherapies, the participants underwent low-dose lymphodepletion, followed by a single infusion of Miv-cel at a target dose of 1 x 10⁸ CAR T-cells and followed up for 12 months (median 6.5 months).

The median follow-up was 6.5 months, and at 16 weeks, the median timed 25-foot walk (T25FW) had improved by 45.6%, from a median of 11.1 seconds at baseline.

The presenter pointed out that 81% of patients achieved a “clinically meaningful improvement,” defined as a reduction on the T25FW of at least 20%, and 31% of patients completed the T25FW in less than 5 seconds, which is “comparable to a typical time for a healthy adult,” she remarked.

Twelve of the patients required walking aids to complete the T25FW at baseline, but by week 16 this was only necessary for four patients.

Piquet also noted that at 16 weeks and up to the last follow-up all the patients remained free of immunomodulatory or immunosuppressant SPS therapy.

Miv-cel showed treatment benefit across secondary endpoints at 16 weeks as well, including significant improvements in disability on the modified Rankin Scale, mobility on the Hauser Ambulation Index, and significant reductions in Distribution-of-stiffness Index and Heightened Sensitivity Scale scores.

“Importantly, 96% of patients had improvement in at least one primary or secondary efficacy endpoint,” said Piquet.

With regards to safety, she reported that Miv-cel was “well-tolerated” and the safety profile was “manageable.”

The most common adverse events (AEs) were grade 1 or 2 cytokine-release syndrome (CRS; 92%), fatigue (54%), diarrhea (38%), and headache (31%).

Grade 3 or 4 neutropenia occurred in 15% of patients, and 12% of patients had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS; all grade 1). There were no cases of high-grade CRS or ICANS, commented Piquet.

Treatment-related serious AEs occurred in three patients, all of which resolved without lasting effects.

Piquet concluded that “Miv-cel demonstrates the potential to deliver durable, drug-free, disease-free remission, reverse disability, and change the SPS treatment paradigm.”

When asked about the scalability of the treatment outside of specialized centers, the presenter said that the use of CAR T-cell therapy in neurology is going to be a “learning curve,” and that “working closely with hematologists is going to be important.” But she believes that this type of therapy “has potential for many autoimmune neurologic diseases.”

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78th AAN Annual Meeting; Chicago, Illinois, USA: 18–22 April 2026