KYV-101 helps 2 hard-to-treat progressive MS patients: Case study

Treatment addresses 'one of the most difficult challenges in MS therapy'

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by Steve Bryson, PhD |

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Kyverna Therapeutics‘ cell-based therapy KYV-101 had an acceptable safety profile and promising treatment effects when given to two people with hard-to-treat progressive multiple sclerosis (MS), according to a case study.

“We are very pleased about offering this potentially paradigm-shifting treatment opportunity to patients that have exhausted other medical recourses,” senior co-author Christoph Heesen, MD, professor for clinical and rehabilitative MS research at the University Medical Center Hamburg-Eppendorf, said in a Kyverna press release.

“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,” Heesen said. The central nervous system is comprised of the brain and spinal cord.

The case study, “CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis,” was published in the journal Med.

MS is marked by immune-mediated damage to healthy parts of the spinal cord and brain. More than 20 therapies are approved for relapsing forms of MS, but far fewer options exist for people with progressive and nonactive disease forms.

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Targeting B-cells for elimination

KYV-101 is designed to ease MS and other autoimmune conditions by eliminating B-cells, immune cells that generate self-reactive antibodies that mistakenly target healthy tissues and drive these disorders.

Treatment involves collecting a patient’s immune T-cells and modifying them in a lab to produce a chimeric antigen receptor (CAR) that selectively binds to CD19, a protein found at the surface of B-cells. Modified T-cells are then expanded in the lab and infused back into the patient with the goal of eliminating CD19-producing B-cells.

Researchers at Stanford University teamed up with Kyverna in March to conduct an investigator-initiated, open-label Phase 1 trial (NCT06138132) to test KYV-101 in as many as 12 people with primary progressive MS (PPMS) or secondary progressive MS (SPMS) who have not experienced recent relapses.

In January, the U.S. Food and Drug Administration (FDA) cleared the launch of an open-label, Phase 2 clinical trial called KYSA-7 to evaluate KYV-101 in a similar patient population.

Heesen and colleagues in Germany tested the feasibility and safety profile of KYV-101 in two patients with progressive MS. Both were treated as part of a named patient program, which allows treatment with unauthorized medicines in critically ill patients who fail to respond to conventional therapies.

The first case was a woman with a 23-year history of MS. She was initially diagnosed with relapsing-remitting MS (RRMS) and started taking Ocrevus (ocrelizumab) in 2021 due to progressive neurological deterioration. Despite receiving Fampyra (fampridine), sold in the U.S. as Ampyra, to address walking difficulty, her disease continued to worsen.

Within a few hours of KYV-101 infusion, she developed a recurring fever and was diagnosed with mild cytokine release syndrome (CRS), a large release of inflammatory molecules that can cause potentially life-threatening symptoms, for which she was treated. There were no signs of immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially serious neurotoxic side effect associated with CAR-T cell therapies.

She experienced a temporary worsening of MS-related symptoms due to the fever, which eventually resolved. By day 100, her self-reported walking distance increased from 400 meters to 700 meters. Other neurological assessments remained unchanged.

Blood tests showed a peak expansion of CAR-T cells six and seven days after infusion, which remained detectable up to day 100, and B-cell counts were depleted by day 2. Treatment-related cells were also found in the cerebrospinal fluid (CSF), which surrounds the spinal cord and brain, and resulted in a drop in self-reactive antibodies.

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Progressive MS patient’s disability remained stable

The second case was a male patient diagnosed with PPMS in 2019 after a two-year history of worsening walking abilities and lesions on MRI scans. Despite treatment with Ocrevus, his walking disability worsened.

After the KYV-101 infusion, he showed no signs of CRS or ICANS over 28 days of follow-up, and no other adverse events were noted. No new lesions or neurological symptoms were observed, and his disability remained stable for one month after the infusion.

The patient showed only a modest expansion of CAR-T cells in blood and CSF, but B-cells, which were already undetectable during treatment with Ocrevus, remained so in the bloodstream. Antibody levels in the blood were reduced on day 14 post-infusion, but no changes in the levels of CSF self-reactive antibodies were noted.

“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,” said senior co-author Nicolaus Kröger, MD, professor of clinical and rehabilitative MS research at the University Medical Center Hamburg-Eppendorf.

We are committed to transforming the standard treatment for patients living with multiple sclerosis.

The FDA granted fast-track status to KYV-101 as a potential treatment for progressive MS. Fast track designation is intended to advance the development of therapies that address the unmet medical needs of people with serious or life-threatening conditions.

KIV-101 also is being assessed in other autoimmune disorders, including lupus, myasthenia gravis, and systemic scleroderma.

“We are committed to transforming the standard of treatment for patients living with multiple sclerosis,” said Peter Maag, PhD, CEO of Kyverna. “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.”