Kyverna’s CAR-T KYV-101 Improves Walking Speed in Patient With Stiff-Person Syndrome

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The case study was recently published in the Proceedings of the National Academy of Sciences.

Simon Faissner, MD, a professor for translational neuroimmunology in the Department of Neurology at Ruhr University Bochum, St. Josef Hospital, in Germany

Simon Faissner, MD
Credit: Ruhr University Bochum

Kyverna Therapeutics’ KYV-101, an investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has improved the condition of a patient with stiff-person syndrome (SPS) on several measurements, including walking speed.1 The data comes a case study covering the treatment of a single patient that was recently published in the Proceedings of the National Academy of Sciences.

The patient, a 59-year-old woman whose first symptoms of SPS appeared in 2014, was treated in Germany under a named-patient use basis.1,2 The patient 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.

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.

"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.2 "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."

Faissner and colleagues also noted that the patient experienced a “marked improvement” in stiffness after treatment.1 On the Modified Ashworth scale (MAS), the score for the patient’s right knee had been 2 to 3 at baseline but was reduced to 0 at Day 14. For the patient’s left knee, the MAS score fluctuated around 4, but was noted to improve modestly over time. Pain, which was measured with a numeric rating scale, also showed improvement, with several assessments showing a score of 0 starting at Day 50, down from the baseline score of 4. Furthermore, at Day 112, the patient’s score on the fatigue severity scale had decreased from 48 points at baseline to 40 points.

At Day 56 the patient’s antiGAD65 titers showed 1:1,000 and at Day 144 they showed 1:320, a reduction from 1:3,200 as a recorded at baseline. Faissner and colleagues additionally noted that during the first 5 months posttreatment the patient was able to reduce GABAergic medication use in a stepwise manner, from 25mg, to 10mg, to 5mg. They also pointed out that the patient did not receive any additional immunotherapy, including intravenous immunoglobulin, after being treated with KYV-101.

"On the heels of recent case reports of the use of KYV-101 in multiple sclerosis and myasthenia gravis, we are excited to see positive outcomes of KYV-101 in a patient suffering from SPS," Peter Maag, PhD, the chief executive officer of Kyverna, added to the statement.2 "These data underscore the dedication of the Kyverna village to patient care and scientific advancement."

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. Paracetamol, dexamethasone, and tocilizumab were used to successfully address the adverse event. 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.

Faissner and colleagues concluded that the findings of this study support continued investigation of CD19-directed CAR-T therapy for refractory B-cell–related neuroimmunological disorders. They noted several areas of interest for further study in future clinical trials, including a closer look at the potential activity of KYV-101 in the cerebrospinal fluid, the character of repopulation of B-cells after treatment, and outcomes at longer follow-up times.

"It is remarkable to observe the transformational effects in a patient deemed refractory to available standard treatments,” senior coauthor Ralf Gold, MD, a professor of Medicine and chair of Neurology at Ruhr University Bochum, also added to the statement.2 “With the disease progressing over several years despite the best medical treatment, I recommended the CAR T-cell therapy approach. The absence of observed neurotoxicity and the measured impact on the pathogenic antiGAD65 autoantibodies pave the way for additional studies to confirm the initial, promising findings."

REFERENCES
1. 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: doi.org/10.1073/pnas.2403227121
2. 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. https://ir.kyvernatx.com/news-releases/news-release-details/first-disease-use-kyverna-therapeutics-kyv-101-patient-severe
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