Kyverna’s CAR-T Cleared for Stiff-Person Syndrome Trial


KYV-101 racks up another potential indication in addition to its primary autoimmune investigations.

 Marinos Dalakas, MD, FAAN, Professor of Neurology, Director, Neuromuscular Division, Thomas Jefferson University School of Medicine

Marinos Dalakas, MD, FAAN

Credit: Neuro-Edu

The FDA has cleared Kyverna Therapeutics’ investigational new drug application (IND) to investigate its KYV-101 cell therapy in people with stiff-person syndrome (SPS).1

"CAR T-cell therapy has already shown preliminary but promising results in patients with SPS treated outside of the US," Marinos Dalakas, MD, FAAN, Professor of Neurology, Director, Neuromuscular Division, Thomas Jefferson University School of Medicine, Philadelphia, PA, said in a statement.1 "I find the KYSA-8 trial of extraordinary importance as a promising novel therapy for patients with stiff person syndrome who do not respond to current therapies, with implications in providing potentially long-lasting benefits."

KYV-101 is an autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy originally developed for oncologic use. The therapy is currently being evaluated in sponsored, open-label, early clinical trials in the United States and Germany for lupus nephritis, systemic sclerosis, myasthenia gravis, and multiple sclerosis.

"The IND clearance gives us confidence in our dedication to bringing a potential paradigm shift in the treatment of patients suffering from SPS and reaffirms a target dose of 100 million cells for KYV-101," Sham Dholakia, MD, business unit head rare diseases, Kyverna, added.2 "We are also very grateful to the FDA for the collaborative approach and timely vetting of our clinical trial design."

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The clearance comes just after Kyverna announced the first data of KYV-101 in a patient with SPS earlier this month. The patient, a 59-year-old woman whose first symptoms of SPS appeared in 2014, was treated with a single dose of 1x108 CAR T-cells on Day 0 of the study, after having undergone a lymphodepletion regimen with fludarabine and cyclophosphamide. The patient has been followed for 6 months after treatment.1

The patient’s walking speed increased to 0.83 m/s on Day 20, up more than 100% from 0.37 m/s at Day 1, on the 5.5-m walking test, which was conducted with the patient using a wheeled walker. Furthermore, the patient achieved an uninterrupted walking distance at home of 4km after Day 50 and 6km after Day 90, up from her distance of just several meters recorded at baseline.2

In terms of safety, the patient experienced a grade 2 case of cytokine release syndrome (CRS) that included a fever that reached 38.3°C and transient hypotension which resolved after paracetamol, dexamethasone, and tocilizumab. The case of CRS, which had developed by Day 9, was also accompanied by sore throat and cervical lymph node swelling, both of which also resolved with the aforementioned use of drugs to treat the CRS. Liver transaminases showed transient and limited increases of around 4-fold, with the peak elevation occurring at Day 15, but were spontaneously reversed at Day 45.2

"It is extremely encouraging to see this patient improving the self-reported, uninterrupted walking distance from less than 50 meters to several kilometers within 3 months after treatment," lead coauthor Simon Faissner, MD, a professor for translational neuroimmunology in the Department of Neurology at Ruhr University Bochum, St. Josef Hospital, in Germany, said in a statement."These dramatic improvements—if confirmed by further studies—may eventually provide renewed hope for a much-needed paradigm shift in the treatment of debilitating autoimmune diseases."

1. Kyverna's KYV-101 Receives U.S. FDA IND Clearance for Treatment of Patients With Treatment-Refractory Stiff-Person Syndrome in the KYSA-8 Phase 2 Trial. News release. Kyverna Therapeutics. June 20, 2024.
2. Faissner S, Motte J, Sgodzai M, et al. Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome. Proc Natl Acad Sci USA. 2024;121(26):e2403227121. doi:
3. First-in-disease use of Kyverna Therapeutics' KYV-101 in patient with severe stiff-person syndrome published in proceedings of the national academy of sciences (PNAS). News release. Kyverna Therapeutics, Inc. June 17, 2024. Accessed June 18, 2024.
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