CAR-T Therapy KYV-101 Achieves Durable Response in Phase 2/3 KYSA-6 Trial of Myasthenia Gravis

Recently reported data from the phase 2 portion of the KYSA-6 trial (NCT06193889) showed that treatment with investigational KYV-101 (Kyverna Therapeutics), a CD19 CAR T-cell therapy, led to clinically meaningful responses in efficacy end points for patients with generalized myasthenia gravis (gMG). Overall, the data reinforced the potential of this novel therapeutic, which continues to be studied in the ongoing phase 3 portion of KYSA-6.^1,2

The trial, which was previously a pahse 2 study but amended to phase 2/3 included patients aged 18-75 with gMG, a history of AChR or Muscle-Specific Kinase (MuSK) autoantibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 6. Presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held October 29 to November 1, in San Francisco, California, the presentation featured 6 patients with moderate to severe gMG, and an average disease duration of 5.3 years (range, 1.7-13.3) who were treated with a single dose of 1x108 KYV-101 CAR T-cells.

At data cut-off, or up to 36 weeks, all 6 patients achieved clinically meaningful, robust, rapid, and sustained reductions in MG-ADL, and Quantitative Myasthenia Gravis (QMG) score, the primary outcomes, regardless of prior biologic exposure. Specifically, treated patients demonstrated mean reductions of –8.0 points on MG-ADL and –7.7 points on QMG at 24 weeks, with impacts observed as early as 2 weeks post-infusion.

"These unprecedented results validate our Phase 3 trial design and underscore KYV-101’s potential to deliver durable, drug-free, disease-free remission by targeting the disease at its source through deep B-cell depletion," Naji Gehchan, MD, MSc, chief medical and development officer at Kyverna, told NeurologyLive. “We’re eager to continue this progress to help address unmet needs for patients living with generalized myasthenia gravis."

Efficacy data showed that all patients (n = 6) achieved at least a 3-point reduction in both MG-ADL and QMG, in addition to all patients achieving clinically meaningful response on Myasthenia Gravis Composite (MGC) scores. At 12 weeks, patients showed a mean reduction of –12 points on MGC, all while being free of nonsteroidal immunosuppressants, high-dose steroids, and FcRn and complement inhibitors.

In terms of safety, KYV-101 was shown to be well-tolerated, with no new safety signals and one case of a serious adverse event (AE; grade 4 neurotropenia), which improved with standard supportive care and was downgraded to grade 1 at data cut-off. Notably, patients on the CAR T-cell therapy did not experience any high-grade cytokine release syndrome, as well as no immune effector cell-associated neurotoxicity syndrome events throughout the study period.

Gehchan added, "While there are many approved therapies and new therapies under development for gMG, none have been able to address the underlying disease on a mechanistic level. With KYV-101, we are taking a novel, upstream approach to directly target the disease source by tapping into the patient’s own immune cells to fight disease."

He continued, "As an investigational CAR T-cell therapy, KYV-101 directly targets the disease source by deeply depleting the autoreactive B-cells in tissues. In addition, KYV-101 has been shown to have a positive impact on a broader set of immune cell types, and in particular, regulatory T-cells, which are essential for keeping the immune system in check."

READ MORE: New Phase 3 Study to Evaluate Remibrutinib in Generalized Myasthenia Gravis Treatment

KYV-101, which continues to be studied in other diseases like progressive multiple sclerosis, received regenerative medicine advanced therapy (RMAT) designation by the FDA in August 2024, further recognizing it as a promising treatment for gMG. The CAR in KYV-101 was designed by the National Institutes of Health to improve tolerability and was tested in a phase 1 trial (NCT02659943) in oncology with results published in Nature in 2020.³

The first-in-human study enrolled 20 patients with B-cell lymphoma and was designed primarily to evaluate safety and feasibility, with secondary assessments focused on blood levels, anti-lymphoma activity, the potential for second infusions, and immunogenicity. At the time known simply as the Hu19-CD828Z T-cell therapy, KYV-101 met all of its study objectives. Patients treated with the therapy showed lower cytokine levels compared with those who received FMC63-28Z T cells, a finding investigators suggested could account for the reduced neurologic toxicity observed with the agent.

In early 2024, Kyverna reported the first individual treatments with KYV-101 in two patients with progressive MS. The therapy was well tolerated in the short term, showing CAR-T cell expansion in the CSF without neurotoxicity, and a reduction in intrathecal antibody production in one patient. Although both had previously received ocrelizumab, circulating B cells were detected only in patient 1, whose remaining B-cell population was depleted by day 2 and remained absent through day 100. Patient 1 also experienced a drop in oligoclonal bands from 13 to 6 by day 64, while patient 2 showed no changes in OCBs or intrathecal immunoglobulin levels.⁴

In concluding thoughts, Gehchan went on to note, "We believe KYV-101's clinical profile provides us with an advantage.We anticipate a large effect size based on the first patients in the compassionate use pathway that has now been confirmed in this interim Phase 2 readout. This enables us to have a more efficient study design with only ~60 patients to be randomized between standard of care and KYV-101. We are also including important PK and PD endpoints like B cell depletion and looking at effects on immune cell populations to help support our mechanistic approach that complement the other outcome assessments."

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REFERENCES
1. Kyverna Therapeutics Announces Positive Interim Phase 2 Data from KYSA-6 Study of KYV-101 in Generalized Myasthenia Gravis at AANEM 2025. News release. Kyverna Therapeutics. October 29, 2025. Accessed November 19, 2025. https://ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-announces-positive-interim-phase-2-data
2. Muppidi S, Hunter MC, Hoffmann S, et al. Update on the phase 2 part of KYSA-6, an open-label, single-arm, multicenter study of KYV-101, a fully human CD19 chimeric antigen receptor T-cell therapy in generalized myasthenia gravis. Presented at: 2025 AANEM Annual Meeting. October 29-November 1; San Francisco, CA. ABSTRACT 106.
3. Bruno JN, Lam N, Vanasse D, et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nature. 2020;26:270-280. doi:10.1038/s41591-019-0737-3
4. Fischbach F, Richter J, Pfeffer LK, et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Cell Press. Published March 29, 2024. doi:10.1016/j.medj.2024.03.002.