Evaluating CAR-T Miv-Cel in Myasthenia Gravis

The emergence of CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy as a potential intervention in antibody-mediated autoimmune diseases, such as myasthenia gravis (MG), has opened a fundamentally new therapeutic avenue in neurology. The mechanistic rationale centers on deep depletion of CD19-expressing B cells through a single treatment course, with the goal of achieving a durable immune reset.

Mivocabtagene autoleucel (miv-cel; KYV-101; Kyverna Therapeutics) is an investigational autologous, fully humanized anti-CD19 CAR-T therapy currently being evaluated for the treatment of MG. Srikanth Muppidi, MD, a clinical professor of adult neurology at Stanford University and a specialist in neuromuscular disorders with a particular focus on MG, recently presented phase 2 data from the KYSA-6 clinical trial (NCT06193889) evaluating miv-cel in patients with MG at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18 to 22 in Chicago, Illinois.

NeurologyLive® sat down with Muppidi at the conference to discuss the KYSA-6 phase 2 findings in detail. In the conversation, he reviewed the clinical and mechanistic data observed, including evidence of CAR T-cell expansion, B-cell depletion, and a pattern of selective antibody reduction that may point to immune reset. He also outlined the design of the planned phase 3 randomized trial.

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

Srikanth Muppidi, MD: I specialize in neuromuscular disorders, specifically MG. I had a presentation on the use of CAR-T therapy in MG. It's an exciting field for MG, with multiple presentations in advancing therapy in MG.

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

I was able to present the phase 2 data of the KYSA-6 study, which evaluated the CD19-targeted, fully humanized miv-cel product. In 7 patients, after one 1 of miv-cel therapy, we were able to show a robust and dramatic improvement in clinical symptoms and a reduction in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores. Patients were able to tolerate this therapy, and there were no concerning safety signals.

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

CAR T-cell therapy promises a new innovation and a new way of thinking about treating autoimmune diseases, especially autoimmune diseases that have B-cells as the primary pathogenic process. The degree and the depth of improvement that we are seeing in patients could potentially translate to a completely life-changing way of dealing with the disease. We are at the leading edge of this new development, and it is very gratifying to see the kind of treatments that we are able to offer to patients with MG. I am quite optimistic that further studies will definitely consolidate the findings that we have and prove the concept that this is the way to treat refractory, difficult-to-treat patients.

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

Some of the unanswered questions that we have in the field are, for example, how long the benefit would last. We clearly know that 1 dose of CAR-T therapy clearly makes a big difference. We don't quite know how long the benefit lasts for. We are optimistic that it will be sustained for at least 1 or 2 years, if not longer—so that part has not been completely answered.

There are also different CAR-T targets being studied, and we certainly don't have any comparative data on that yet either. In addition, since CAR-T therapies are only recently being used in autoimmune diseases, we will need long-term follow-up for safety.

What are the next steps for the miv-cel program in myasthenia gravis?

For miv-cel,, we are going to present our plan for a phase 3 clinical trial. This is going to be a randomized trial where patients will either get miv-cel or continue on the standard of care they are already on, with an opportunity to get miv-cel after 6 months. This will be the first randomized clinical trial for a DNA CAR-T with a blinded evaluator. The field is definitely moving toward trying to get approval for these therapies for autoimmune diseases, including MG—and for me, that is probably the most exciting thing.

Is there anything else you want to add?

In the phase 2 data, we were additionally able to show a very nice expansion of the CAR T-cells with B-cell reduction, and we were also able to show a clear reduction in antibody levels. But at the same time, protective antibodies against infections—especially viral infections and vaccination responses—remains robust. This raises the possibility that there is likely some type of immune reset that’s happening, because patients have a reduction in pathogenic antibodies, but not in the protective antibodies. We are hopeful that this will continue to replicate in the phase 3 trial.

Beyond miv-cel, I am optimistic for the field that CAR-T therapy certainly offers a new paradigm for how we would treat refractory antibody-mediated diseases. In many ways, neurology is at the forefront of this development, and I am excited for the field, for the faculty, and for the patients who are involved in these trials.

This transcript has been edited for clarity.