Kyverna Therapeutics reports positive Phase 2 KYSA-8 data showing miv-cel improves mobility and reduces treatment burden in stiff person syndrome.
Written By: Vennela Reddy, BPharm
Reviewed By: Pharmacally Editorial Team
Kyverna Therapeutics has reported positive primary analysis results from its registrational Phase 2 KYSA-8 trial evaluating mivocabtagene autoleucel (miv-cel, KYV-101), a CD19-targeting autologous CAR T-cell therapy, in patients with stiff person syndrome (SPS), with findings presented at the American Academy of Neurology Annual Meeting. The single-arm study enrolled 26 patients with inadequate response or intolerance to off-label immunomodulatory therapies, each receiving a single infusion of 1×10^8 CAR T cells.
At 16 weeks, the trial met its primary endpoint, showing a statistically significant 46% median improvement in mobility as measured by the Timed 25-Foot Walk (p=0.0003), with 81% of patients achieving at least a 20% clinically meaningful improvement. Among those requiring walking aids at baseline, 67% no longer needed assistance, and nearly one-third reached walking speeds comparable to healthy adults. All participants discontinued chronic immunotherapies through follow-up, an outcome not previously reported in SPS.
Secondary endpoints demonstrated significant improvements across disability, stiffness, hypersensitivity, and mobility measures, while exploratory findings showed deep but transient B-cell depletion and reductions in GAD65 autoantibody titers, consistent with the therapy’s mechanism of action. These biological changes were accompanied by improvements in physical and mental functioning, including performance on the 6-Minute Walk Test and patient-reported outcomes, indicating broader functional benefit.
Miv-cel demonstrated a manageable safety profile, with no high-grade cytokine release syndrome or neurotoxicity observed; grade 3/4 neutropenia was manageable, and all treatment-related serious adverse events resolved without long-term sequelae, supporting the potential for outpatient administration.
Lead investigator Amanda Piquet indicated that SPS is a progressive autoimmune disorder with limited effective treatment options and that the observed reductions in disability, stiffness, and hypersensitivity, alongside improved mobility, represent a meaningful clinical advance.
Warner Biddle Chief Executive Officer of Kyverna stated that the findings support the potential of a one-time CAR T-cell therapy to alter disease course and reduce long-term treatment burden, with preparations underway for a biologics license application.
Naji Gehchan M.D., Chief Medical and Development Officer of Kyverna emphasized that the therapy is designed to enable a broad immune reset through B-cell depletion with the aim of durable, treatment-free remission.
A retrospective natural history analysis of 153 patients presented alongside the trial highlighted the limited efficacy of current off-label therapies, with most patients showing minimal improvement in walking ability and increasing reliance on assistive devices over time, underscoring the unmet need in SPS, a rare autoimmune neurological disorder affecting approximately 6,000 individuals in the United States
Reference
About the Writer
Vennela Reddy, B.Pharm is a pharmacy graduate with a keen interest in clinical research, pharmacovigilance, and medical writing, with a growing focus on publishable and scientific content development. In her words, she is passionate about translating complex medical data into clear, evidence-based communication.