Design of KYSA-6, a Phase 2, Open-label, Multicenter Study of KYV-101, a Novel Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Refractory Generalized Myasthenia Gravis
Aiden Haghikia1, Dominic Borie2, James Chung2, Ralf Gold3
1Department of Neurology and Clinical Neurophysiology, Hanover Medical School, 2Kyverna Therapeutics Inc., 3Department of Neurology, Ruhr University Bochum
Objective:
To evaluate the safety and efficacy of KYV-101 in patients with refractory generalized myasthenia gravis (MG).
Background:
MG is a B-cell-mediated autoimmune disease for which new therapeutic paradigms are needed that can improve disease activity in refractory patients and enable sustained treatment-free remission. KYV-101 is a first-in-class, fully human autologous anti-CD19 CAR T-cell therapy with a promising clinical safety profile. In the named patient setting, KYV-101 demonstrated rapid, profound improvements in disease severity and was well-tolerated in patients with severe refractory MG. In a case study of a patient with treatment-refractory, anti-acetylcholine receptor (AChR) positive generalized MG, a single infusion of KYV-101 resulted in rapid improvement of symptoms and mobility (Haghikia A, et al. Lancet Neurol. 2023;22:1104-1105). KYV-101 is being investigated in KYSA-6 (NCT06193889), a phase 2 open-label, multicenter study in MG. KYV-101 received FDA Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designation for MG.
Design/Methods:
Twenty patients 18–75 years old, with generalized MG (class IIB-IV per MG Foundation of America), the presence of disease-related autoantibodies, an MG-ADL score ≥6, who failed prior immunosuppressive/immunomodulatory therapy, are eligible. After lymphodepletion (fludarabine 30 mg/m2/day, cyclophosphamide 300 mg/m2/day; 3 days), patients will receive a single infusion of KYV-101 at the target dose of 1×108 CAR T cells. Primary endpoints are the safety and efficacy of KYV-101, assessing adverse events and MG Activities of Daily Living (MG-ADL) at 24 weeks. Secondary endpoints include evaluation of further efficacy, disease-related autoantibodies, and patient-reported outcomes.
Results:
KYSA-6 is ongoing in the US and Germany.
Conclusions:
KYV-101 is a novel therapy with the potential to change the treatment paradigm through deep B-cell depletion and immune reset with a single infusion in patients with B-cell driven autoimmune diseases like MG. KYV-101 is also under investigation in additional neurologic and rheumatologic diseases.
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