MGFA Session 2025: Single dose of KYV-101 eases gMG symptoms
Early clinical trial data show rapid, lasting reductions in severity for 6 adults
A single dose of KYV-101, a cell therapy being developed by Kyverna Therapeutics for generalized myasthenia gravis (gMG), led to rapid and sustained reductions in symptom severity — lasting up to six months thus far — in adults with gMG.
That’s according to data from an interim analysis covering six patients who took part in the first portion of a Kyverna-sponsored Phase 2/3 clinical trial dubbed KYSA-6 (NCT0619388), which is assessing the treatment’s safety and effectiveness in adults with gMG. The company recently aligned with the U.S. Food and Drug Administration about the trial’s Phase 3 portion, which Kyverna says may offer a path to regulatory approval.
“With today’s results, we are setting a new standard across key clinical outcome measures for gMG, particularly in the depth and durability of response achieved with just a single dose of KYV-101,” Warner Biddle, CEO of Kyverna, said in a company press release that noted that all study participants to date have seen clinically meaningful responses to the treatment.
“Patients experienced rapid and unprecedented symptom improvement without the need for ongoing background therapy,” Biddle said. “These compelling data build upon our previously reported compassionate use experience, further advancing our goal to deliver durable, drug-free, disease-free remission, and importantly, reinforce our confidence in the KYSA-6 Phase 3 trial design.”
Srikanth Muppidi, MD, a professor of adult neurology at Stanford Medicine and a trial investigator, presented the new results during the Myasthenia Gravis Foundation of America (MGFA) scientific session at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting, held last week in San Francisco. The presentation was titled “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.”
Ongoing trial testing KYV-101 in people with hard-to-treat gMG
Immune attacks driven by self-reactive antibodies — ones that disrupt nerve-muscle communication — are the root cause of myasthenia gravis (MG), an autoimmune disease marked by symptoms of muscle weakness and fatigue. Disease-causing antibodies are produced by immune cells called B-cells.
In gMG, symptoms affect muscle groups throughout the body, and they don’t always respond to treatment.
“In spite of many of the novel therapies that are available and being developed, there are still patients who have inadequate [symptom] control,” Muppidi said.
KYV-101 is a cell therapy designed to eliminate B-cells and reduce the production of MG-causing antibodies, thereby easing disease symptoms. It uses T-cells, a type of immune cell that can kill other cells, which are collected from the patient who is meant to receive treatment. The harvested T-cells are then engineered in a lab to be equipped with a chimeric antigen receptor (CAR) that instructs them to target a specific protein on B-cells. After this process, the modified cells are returned to the patient to attack and eliminate B-cells.
KYSA-6’s Phase 2 portion tested KYV-101 in adults with the most common types of gMG-causing antibodies. Eligible patients had failed to respond to at least two immunosuppressive or immunomodulatory therapies, or to at least one immunosuppressive therapy and required chronic plasmapheresis, known as plasma exchange, or intravenous immunoglobulin therapy, called IVIG, to control symptoms.
All patients received a single infusion of KYV-101 containing 100 million CAR T-cells.
The interim results covered the first six trial participants, three of whom had undergone at least 24 weeks, or approximately six months, of observation after the infusion.
“All patients had robust CAR T expansion and B-cell depression after treatment,” Muppidi noted.
Two weeks after receiving KYV-101, participants experienced a clinically meaningful reduction in symptom severity, as evidenced by a decrease in the scores of two validated measures of disease severity: the MG Activities of Daily Living, or MG-ADL, and the Quantitative MG scales, known as QMG. The mean reduction in both scores was 7.8 points, with all participants exceeding thresholds for clinical relevance, according to the data.
5 of 6 patients remained off other treatments at latest follow-up
The three participants who had reached week 24 post-infusion saw their MG-ADL scores drop by a mean of 8 points, while QMG scores were reduced by a mean of 7.7 points. Two participants also achieved minimal symptom expression, corresponding to an MG-ADL score of 0 or 1.
“One important distinguishing feature, compared to a lot of the novel therapies that have been approved [or] are being tested, is that when these patients are discharged after the CAR T [infusion], they’re essentially off most of their baseline immunosuppressive therapy,” Muppidi said. The researcher noted that five of the six participants remained free of these other therapies at their most recent follow-up.
“Interim results showed that KYV-101 has the potential to deliver rapid, substantial and clinically meaningful improvements … for 100% of patients with a single dose, while also offering the potential for patients to become symptom-free.
KYV-101 was generally well tolerated by the patients. There were no severe events of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, which are serious conditions that sometimes arise following CAR T-cell treatment.
Three participants experienced serious neutropenia, or low levels of immune neutrophil cells, which normally help fend off infections. Two of these cases were resolved within 10 days, while the other had a manageable case that eased over time.
Naji Gehchan, MD, Kyverna’s chief medical and development officer said the company is preparing for the next stage of the trial.
“We look forward to initiating enrollment for the Phase 3 portion of the trial by the end of this year, as well as sharing updated data from the Phase 2 portion of the trial next year,” Gehchan said, noting that, to date, “all patients [are] exceeding the thresholds for our Phase 3 co-primary” goals.
“Interim results showed that KYV-101 has the potential to deliver rapid, substantial and clinically meaningful improvements … for 100% of patients with a single dose, while also offering the potential for patients to become symptom-free,” Gehchan said.
Note: The Myasthenia Gravis News team is providing virtual coverage of Myasthenia Gravis Foundation of America’s scientific session at the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting Oct. 29. Go here to see the latest stories from the conference.
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