CAR-T therapy improved mobility and stiffness in stiff person syndrome in a pivotal Phase II study.
CAR-T Therapy in Stiff Person Syndrome
CAR-T therapy delivered significant clinical improvements in adults with stiff person syndrome (SPS) in the pivotal multicenter Phase II KYSA-8 study presented at AAN 2026 in Chicago, Illinois, USA. In a disease with no approved treatments and substantial long-term disability, a single infusion of miv-cel was associated with rapid gains in walking speed, reduced stiffness, and continued freedom from immunomodulatory therapy at last follow up.
SPS is a progressive autoimmune neurologic disorder marked by muscle stiffness and painful spasms that can severely impair mobility. Investigators evaluated miv-cel, an autologous CD19 CAR-T-cell therapy with CD28 co-stimulation, in adults whose disease had responded inadequately to prior immunomodulatory treatment.
Rapid Mobility Gains Reported
Twenty-six patients received lymphodepletion with fludarabine and cyclophosphamide over 3 days, followed by a single infusion of miv-cel at a target dose of 1×10⁸ CAR-T cells. The primary endpoints were change from baseline to Week 16 in timed 25-foot walk and safety.
The primary efficacy endpoint was met. At Week 16, patients showed a significant median improvement of 4.8 seconds in timed 25-foot walk, representing a 45.6% median improvement from baseline (p=0.0003). Among the 16 patients who reached Week 24, improvement remained sustained, with a median 44.4% gain.
Secondary outcomes also moved in the same direction. Significant Week 16 improvements were reported across modified Rankin scale, stiffness index, heightened sensitivity scale, and Hauser ambulation index, all with p<0.0001.
Safety Profile Supports Further Follow Up
The most common Grade 3 or 4 treatment related adverse event was neutropenia, seen in 15.4% of patients. Low grade cytokine release syndrome occurred in 92.3% of patients, including Grade 1 events in 38.5% and Grade 2 events in 53.8%. Immune effector cell associated neurotoxicity syndrome was reported in 11.5%, with all cases Grade 1. All resolved without sequelae.
Investigators also observed deep B-cell depletion associated with immune reset. Notably, all treated patients remained free of immunomodulatory therapies for SPS at last follow up. With long term follow up ongoing, these results position miv-cel as a potentially important treatment advance for a rare disease with major unmet need.
Reference
Piquet AL et al. Miv-cel CD19 CAR T-Cell Therapy Shows Efficacy and Safety in Stiff Person Syndrome in a Pivotal, Multicenter, Phase 2 Study (KYSA-8). Abstract. AAN Annual Meeting, 18-22 April, 2026.
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