Assessing CAR-T Miv-Cel in Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare, chronic autoimmune neurological disorder defined by progressive axial and limb rigidity and episodic, stimulus-sensitive muscle spasms that can severely impair ambulation and quality of life. Despite its debilitating course, SPS has no FDA-approved disease-modifying therapy, and current management relies primarily on off-label use of benzodiazepines, baclofen, and intravenous immunoglobulin (IVIG) — approaches that provide symptomatic relief for some patients but do not halt disease progression.

Against this backdrop, the emergence of CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy as a potential immunomodulatory intervention has generated considerable interest across the autoimmune neurology community. Mivocabtagene autoleucel (miv-cel; KYV-101; Kyverna Therapeutics) is an autologous, fully humanized anti-CD19 CAR T-cell therapy that has been under investigation in several antibody-mediated autoimmune neurological conditions, including SPS and myasthenia gravis. Amanda Piquet, MD, director of the Autoimmune Neurology Program and holder of the Celine Dion Foundation Endowed Chair in Autoimmune Neurology at the University of Colorado, has been a leading investigator in the clinical evaluation of miv-cel in SPS and recently presented pivotal phase 2 clinical trial data at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18 to 22 in Chicago, Illinois.

NeurologyLive® sat down with Piquet at the conference to learn more about the findings. She reviewed the trial design and patient population, walked through the primary and secondary end point results, addressed the safety profile observed to date, and reflected on what these data mean for a patient community that has long been without approved treatment options.

NeurologyLive: Could you give some background context about what you presented?

Amanda Piquet, MD: I presented the phase 2 registrational single-arm clinical trial using miv-cel in SPS. Miv-cel is an antiCD19 CAR T-cell therapy. SPS is a rare autoimmune neurologic disorder that is progressive. We see patients with progressive stiffness and episodic muscle spasms. We are essentially using an autologous therapy, meaning a patient's own immune cells, their T-cells, to target their B-cells and cause an immune reset in order to treat the autoimmune disease.

Can you give an overview of the key data you presented?

This was a trial of 26 patients with SPS. All patients were refractory to at least 1 immune therapy. Our primary outcome measure was a 25 foot walk, or change from baseline to 16 weeks in the 25 foot walk. We looked at additional measures of secondary end points, including disability, disease-specific outcome measures, including the Distribution of Stiffness Index, as well as the Hypersensitivity Scale.

Our primary end point was the 25-foot walk. We saw a 46% median improvement in that 25-foot walk. Just to put that in perspective, an improvement that is considered clinically significant in the clinic is 20%, and we saw 46%. Additionally, 12 patients required walking assistance at baseline for the 25-foot walk, and at 16 weeks, 63% did not require assistance.

We also looked at measures of stiffness and disability using the modified Rankin Scale and the Hauser Ambulation Index (another scale for walking), and we saw improvements across all of those measures. Between the primary and secondary end points, 96% of patients had an improvement in at least 1 of those end points.

What are the big-picture implications you would want clinicians to take away from these findings?

Miv-cel demonstrated both efficacy and safety in SPS. We didn't see anything unexpected in terms of safety concerns—there was no high-risk cytokine release syndrome (CRS), there was no high-risk immune effector cell–associated neurotoxicity syndrome (ICANS).

This was a highly effective therapy for patients just at Week 16. During the presentation, we showed videos of patients using a walker at baseline and essentially putting that walker aside and being able to walk quickly and normally down the hallway. It was just incredible to see that outcome. We just don't see that with our current off-label use of therapies in this disease today. I think this trial is pivotal, and the results are unprecedented—and it's going to be incredible for the SPS community.

Are there unanswered questions or areas of interest for further research?

What I presented was the 16-week primary outcome. The data cutoff was the end of November of last year, so the follow-up went out to 6.5 months. The total trial is 12 months, so it's going to be important to see the longer-term data come out, and we'll be following the durability of this response.

Is there anything else you want to add?

Let me just go through SPS some more. This is a chronic autoimmune disease and this is a disease that progresses. Patients have walking problems because of their stiffness and because of these episodic muscle spasms. As of today, we have no FDA-approved therapies for this disease and so oftentimes we're reaching for something called IVIG, which is used off-label.

We also had the opportunity at AAN to present on some natural history data, as well—a multicenter study with myself and Scott Newsome, DO, at Johns Hopkins. This is one of the largest datasets that we have for natural history data, and it really looked at what we see with the 25-foot walk, as well as disability, really demonstrating both the progressiveness of this disease and the ineffectiveness of our current therapies.

This transcript has been edited for clarity.