Kyverna’s CAR T Seems Feasible in Multiple Sclerosis

KYV-101 chimeric antigen receptor (CAR) T-cell therapy had a manageable safety profile and demonstrated expansion-dependent effects of CAR-T cells on CD19+ target cells in the central nervous system of patients with multiple sclerosis (MS).¹

"We are very pleased about offering this potentially paradigm-shifting treatment opportunity to patients that have exhausted other medical recourses," senior coauthor Christoph Heesen, MD, professor, clinical and rehabilitative MS research, University Medical Center Hamburg-Eppendorf in Hamburg, Germany, said in a statement.² "Emerging findings indicating that this approach may affect disease biology in the central nervous system are promising, as preventing disease progression remains one of the most difficult challenges in MS therapy."

Researchers from the University Medical Center Hamburg administered the first uses of CAR T-cells in 2 patients with MS. KYV-101 is an autologous, fully human CD19 CAR T-cell therapy being investigated for treating B cell-driven autoimmune diseases. Each patient received a single dose of 1 × 10⁸ of KYV-101 following lymphodepletion with fludarabine.

The construct consists of a CD19 binding domain, a CD8α hinge and transmembrane domain, a CD28 co-stimulatory domain, and a CD3ζ activation domain. The CAR the therapy uses was designed and evaluated by the National Institutes of Health (NIH) for use in oncology.

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"Exploring the safety profile of CAR T administration in this population and hopefully establishing that it compares favorably to hematopoietic stem cell transplant may bring the cell therapy approach to a larger number of patients in need," senior coauthor Nicolaus Kröger, MD, professor of Medicine and medical director, Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, added.² "If safe administration can be replicated in other patients and efficacy be formally established in clinical trials, this may bring a relevant therapeutic option to patients with MS."

The investigators found that both patients that received KYV-101 had acceptable safety profiles, with no immune effector cell-associated neurotoxicity syndrome (ICANS) observed despite detection of CD19 CAR-T cells in the cerebrospinal fluid (CSF). In the first patient, intrathecal antibody production decreased notably in the CSF after CAR-T cell infusion and was sustained through day 64.

"We are committed to transforming the standard of treatment for patients living with multiple sclerosis," Peter Maag, PhD, chief executive officer, Kyverna, added.² "The pioneering work done with KYV-101 by medical teams in Hamburg and in our trials in the U.S. helps build the data backbone needed to further advance our knowledge and hopefully accelerate development of CAR T-cell therapies in autoimmune diseases."

Kyverna recently received clearance of an investigational new drug (IND) application from the FDA for a new clinical trial in patients with MS in the US.³ The open-label phase 2 trial, referred to as KYSA-7, will be one of several clinical trials currently evaluating or in preparation for evaluation of KYV-101 in autoimmune disease. Kyverna is also assessing KYV-101 in lupus nephritis, myasthenia gravis, and systemic sclerosis.

REFERENCES
1. Fischbach F, Richter J, Pfeffer LK, et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med. Published online March 29, 2024. doi: 10.1016/j.medj.2024.03.002
2. First-in-Disease Use of Kyverna Therapeutics' KYV-101 in Patients With Progressive Multiple Sclerosis Published in Med. News release. March 29, 2024. https://www.prnewswire.com/news-releases/first-in-disease-use-of-kyverna-therapeutics-kyv-101-in-patients-with-progressive-multiple-sclerosis-published-in-med-302103748.html
3. Kyverna’s KYV-101 receives U.S. FDA clearance for treatment of patients with refractory, progressive multiple sclerosis in the KYSA-7 phase 2 trial. News release. Kyverna Therapeutics, Inc. January 4, 2024. Accessed January 8, 2024. https://kyvernatx.com/press-releases/kyvernas-kyv-101-receives-u-s-fda-clearance-for-treatment-of-patients-with-refractory-progressive-multiple-sclerosis-in-the-kysa-7-phase-2-trial/