In a single-arm registrational Phase 2 trial (KYSA-8) in 26 patients with stiff person syndrome (SPS), a one-time infusion of the autologous CD19 CAR T miv-cel (KYV-101) delivered a median 46% improvement from baseline in the Timed 25-Foot Walk at Week 16 (p=0.0003). Eighty-one percent achieved a clinically meaningful ≥20% improvement; among 12 patients using a walking aid at baseline, 67% no longer needed assistance at Week 16. All patients discontinued chronic immunotherapies through last follow-up. Secondary endpoints improved significantly (all p<0.0001) with mean changes in mRS (-0.8), HAI (-1.6), DSI (-1.5), and HSS (-3.2). Safety featured no high-grade CRS or ICANS; Grade 3/4 neutropenia occurred in four patients and three patients had serious treatment-related adverse events, all resolved. Median follow-up was 6.5 months (range 4.4–12.2). Kyverna Therapeutics reported these primary analysis results at AAN and positioned them to support a planned BLA for SPS, where no therapies are approved and off-label IVIg and anti-CD20 agents dominate practice. The trial dosed patients at 1×10^8 CAR T cells following low-dose cyclophosphamide/fludarabine. Exploratory data indicated deep, transient B-cell depletion with reductions in GAD65 autoantibodies and improvements on 6-MWT and SF-36. In parallel, a multicenter natural-history analysis of 153 SPS patients on standard care showed minimal improvement in T25FW over time, reinforcing the unmet need and offering contextual evidence for the single-arm design. Strategically, Kyverna is using SPS as a focused entry point for autoimmune CAR T, selecting a high-severity, under-served neuroimmunology indication where a large, durable functional signal can carry regulatory weight despite a modest sample size. The choice of T25FW, complemented by disability and stiffness measures, aims to balance clinical meaningfulness with operational feasibility in a rare disease. The safety profile—no high-grade CRS/ICANS under a low-intensity lymphodepletion regimen—supports the company’s contention that administration could shift toward outpatient settings, a key differentiator for neurology practices not traditionally configured for oncology-style CAR T workflows. [adrotate group="1"] If regulators accept the magnitude and consistency of effect—along with the natural-history backdrop—this could set a template for autologous CD19 CAR T development in rare autoimmune neurologic conditions. It also raises competitive pressure across the off-label IVIg and rituximab ecosystem, where chronic dosing, access constraints, and IVIg supply variability create friction. For hospitals and infusion centers, a one-time cell therapy could alter revenue mix and capacity planning. For sponsors and CROs, it signals increased viability of single-arm registrational programs in ultra-rare neuro indications, provided endpoints are tightly linked to function and disability and supported by robust external data. Site-level implications are immediate. Neurology centers will need CAR T readiness—apheresis coordination, cell handling, cytokine/neurotoxicity monitoring pathways, and cross-disciplinary staffing with heme-onc and ICU backup—even if severe toxicities remain infrequent. Referral patterns may consolidate around centers capable of both autoimmune care and cell therapy operations. Vendors focused on vein-to-vein orchestration, analytics for external controls, and post-infusion monitoring could find expanded roles as trials migrate into neurology. [adrotate group="1"] The key watch items now are durability, safety depth, and regulatory posture. Twelve-month outcomes—relapse rates, reinfusion needs, sustained off-therapy status, hypogammaglobulinemia management, and infection burden—will determine approvability and real-world adoption. Regulators will scrutinize the external comparators, endpoint hierarchy, and CMC reliability for an autologous product with potential outpatient use. Operationally, scale-up, slot availability, and time-to-infuse will shape access in a small but dispersed patient population. Beyond SPS, read-through to generalized myasthenia gravis and other B-cell–driven diseases will depend on reproducing a similar efficacy-safety balance in larger, more heterogeneous cohorts. Source link: https://www.globenewswire.com/news-release/2026/04/21/3278588/0/en/Kyverna-Presents-Registrational-Trial-Primary-Analysis-for-Miv-cel-in-Stiff-Person-Syndrome-Demonstrating-Statistically-Significant-Durable-Clinical-Benefit-Across-All-Endpoints-in.html
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
