KYV-101 Achieves Durable Response in Myasthenia Gravis

NeurologyLive® first published this article. This version has been lightly edited.

Recently reported data from the phase 2 portion of the KYSA-6 trial (NCT06193889) show that treatment with investigational KYV-101 (Kyverna Therapeutics), a CD19 chimeric antigen receptor (CAR) T-cell therapy, led to clinically meaningful responses in efficacy end points for patients with generalized myasthenia gravis (gMG). Overall, the data reinforce 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 phase 2 study but amended to phase 2/3, included patients aged 18 to 75 years with gMG, a history of acetylcholine receptor or muscle-specific kinase 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 Annual Meeting, held October 29 to November 1, 2025, 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 cutoff, or up to 36 weeks, the 6 patients achieved clinically meaningful, robust, rapid, and sustained reductions in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores, the dual 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 effects 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, MBA, 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 achieved at least a 3-point reduction in both MG-ADL and QMG, in addition to achieving a clinically meaningful response on Myasthenia Gravis Composite (MGC) scores. At 12 weeks, patients showed a mean reduction of –12 points on their MGC score, all while being free of nonsteroidal immunosuppressants, high-dose steroids, and neonatal Fc receptor and complement inhibitors.

By the data cutoff of the phase 2/3 KYSA-6 trial, all 6 patients achieved clinically meaningful, robust, rapid, and sustained reductions in MG-ADL and QMG scores regardless of prior biologic exposure. | Image Credit: © Herman-stock.adobe.com.jpeg

In terms of safety, KYV-101 was shown to be well tolerated, with no new safety signals and 1 case of a serious adverse event (grade 4 neutropenia), which improved with standard supportive care and was downgraded to grade 1 at data cutoff. Notably, patients on the CAR T-cell therapy did not experience any high-grade cytokine release syndrome or 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.

"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."

KYV-101, which is also being studied for other diseases, including progressive multiple sclerosis, received a regenerative medicine advanced therapy designation from 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, antilymphoma activity, the potential for second infusions, and immunogenicity. At the time known as 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 2 patients with progressive multiple sclerosis. The therapy was well tolerated in the short term, showing CAR T-cell expansion in the cerebrospinal fluid without neurotoxicity and a reduction in intrathecal antibody production in 1 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 (OCBs) from 13 to 6 by day 64, while patient 2 showed no changes in OCBs or intrathecal immunoglobulin levels.4

Gehchan concluded, "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 about 60 patients to be randomized between standard of care and KYV-101. We are also including important [pharmokinetic] and [pharmacodynamic] end points like B-cell depletion and looking at effects on immune cell populations to help support our mechanistic approach that complements the other outcome assessments."

References
1. Kyverna Therapeutics announces positive interim phase 2 data from the 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, 2025; San Francisco, CA. Abstract 106.
3. Brudno 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 Med. 2020;26(2):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. Med. 2024;5(6):550-558.e2. doi:10.1016/j.medj.2024.03.002