AAN 2025: CAR T-cell therapy for MS shows safety, efficacy in trials
KYV-101 tested in PPMS, SPMS patients in 2 Phase 1 studies
Kyverna Therapeutics’ CAR T-cell therapy candidate KYV-101 was deemed safe and well tolerated, and showed preliminary signs of efficacy, in people with progressive forms of multiple sclerosis (MS) in clinical testing.
That’s according to data from two investigator-initiated Phase 1 trials, which enrolled individuals with secondary progressive MS (SPMS) and primary progressive MS (PPMS) who had not experienced recent relapses.
Early findings from both trials were shared in two back-to-back oral presentations at this year’s American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego and online.
In one of the trials, the “[participants] enrolled to date have shown excellent tolerance,” and the therapy demonstrated “robust” effects on some efficacy markers, the investigators wrote in that presentation abstract.
Data presented on first 4 patients given CAR T-cell therapy in trial
MS is caused by immune system attacks that damage healthy parts of the brain and spinal cord. Several immune cells are involved in those attacks, including B-cells, the immune cells that normally produce antibodies to fight off infections.
KYV-101 belongs to a class of treatments called CAR T-cell therapies, which involve collecting a patient’s immune T-cells and engineering them in the lab to carry a man-made receptor — called a chimeric antigen receptor, or CAR — on their surface that makes them more efficient at targeting a specific protein.
The modified T-cells in KYV-101 are particularly designed to target the CD19 protein at the surface of B-cells, allowing them to attack and destroy the disease-causing immune cells once infused back into the patient.
Before cells are infused, however, patients receive a round of chemotherapy to deplete white blood cells and create an environment that is favorable for CAR T-cell expansion and survival.
KYV-101 is being tested in an investigator-initiated open-label Phase 1 trial (NCT06138132) that’s taking place at the Stanford Multiple Sclerosis Center in California. In an open-label study, both participants and researchers know the exact treatment being given.
The trial enrolled 12 patients, ages 18 to 65, with progressive forms of MS.
Now, Jeffrey Dunn, MD, the trial’s principal investigator and chief of neuroimmunology at Stanford University, shared results from the first four patients in a talk at AAN. The presentation was titled “A Phase 1, Open-label, Single Center Study of an Autologous Fully humanized Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy in Subjects with Non-relapsing and Progressive Phenotypes of Multiple Sclerosis.”
Among these four participants, who ranged in age from 47 to 54, were three patients with SPMS and one with PPMS who failed to respond adequately to other treatments. After a round of chemo, three patients received KYV-101 at a dose of 33 million cells, while one was included in a higher dose group and received 100 million cells.
The treatment was well tolerated, according to Dunn, with no reports of cytokine release syndrome, a potentially life-threatening side effect of CAR T-cell therapies marked by an excessive immune response. There were also no signs of severe brain toxicity in treated participants.
Data showed that CAR T-cells were able to expand in the blood and spinal fluid, peaking between 10-21 days after KYV-101 infusion.
Dunn noted that this Phase 1 trial “is not designed to look at clinical benefit.” Nonetheless, the investigator reported that the first treated patient showed a complete eradication of oligoclonal bands, a marker of brain inflammation, at six months. This has not been reported in the literature, he said.
A clinically meaningful reduction in fatigue levels was also reported in the two patients with three-month data.
“We could infuse with well tolerance, the CAR T-cells got into the [brain and spinal cord] in measurable and important ways, they seem to have a measurable immunological effect, and maybe an early clinical effect,” Dunn said. “This represents a very exciting step forward reported in four patients.”
‘Very preliminary evidence’ is positive in Phase 1 clinical study
The second investigator-initiated Phase 1 trial (NCT06451159), which is taking place at the University of California, San Francisco, involves 10 participants with nonrelapsing SPMS or PPMS who are not responding adequately to other MS treatments.
After an initial round of chemo, five are receiving a dose of 33 million cells, and the other five are being given 100 million cells. The trial is funded by Kyverna.
At the AAN meeting, Sasha Gupta, MD, a trial investigator and a professor at the university’s Weill Institute for Neurosciences, shared data from the first two participants. This presentation was titled “An Investigator Initiated Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis.”
The two patients, ages 55 and 63, were both women with SPMS with a fairly high level of disability — according to Gupta, patients who have few treatment options and “are at most need.”
The treatment also had a favorable safety profile in this trial, with no reported brain toxicity. However, the first patient experienced a prolonged and severe reduction in certain immune cells, which required supportive treatment, and the second had cytokine release syndrome manifesting as a mild fever that was easily managed with treatment.
Overall, [KYV-101] has a safe and favorable profile, even in the setting of progressive MS.
CAR T-cells were detected after 14 days both in the blood and spinal fluid in the first woman. This patient also had complete elimination of oligoclonal bands after 43 days and experienced an easing in disability about six months after infusion.
Although there was a repopulation of B-cells at week 12, they were naïve cells, meaning they had not been exposed to molecules that could lead to their activation.
The second patient also showed a proliferation of CAR T-cells at 21 days after treatment, with preliminary data showing a the infused T-cells were working as intended at depleting B-cells.
“Overall, [KYV-101] has a safe and favorable profile, even in the setting of progressive MS,” Gupta said. “We are able to show … very preliminary evidence of CAR-T penetration and potential clearance of compartmentalized inflammation, and that seems to be persistent.”
In addition to these two studies, Kyverna is also running a Phase 2 clinical trial called KYSA-7 (NCT06384976). That trial is comparing KYV-101 against a CD20 antibody in about 120 people with PPMS and SPMS who failed to respond adequately to other therapies.
The main goal is to determine whether the experimental therapy can slow disability progression in these patients. Top-line data is expected in 2027.
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