Kyverna's miv-cel holds one-year benefit in stiff person syndrome as autoimmune CAR-T peers hit safety snags
核心洞察
Kyverna Therapeutics reported one-year topline data from the registrational KYSA-8 trial showing a single dose of miv-cel sustained mobility gains in 26 patients with stiff person syndrome (搜索).
Median improvement on the timed 25-foot walk test reached 49% at 12 months versus baseline, up from 46% at week 16, with a p value below 0.0001.
No high-grade cytokine release syndrome, ICANS or IEC-HS occurred, contrasting with safety holds placed on Novartis's rap-cel and Bristol Myers Squibb (搜索)'s zola-cel autoimmune programs.
Kyverna Therapeutics reported one-year topline durability data from the registrational KYSA-8 trial of miv-cel (mivocabtagene autoleucel (搜索), KYV-101) in stiff person syndrome (搜索) (SPS), alongside longer-term follow-up from the Phase 2 portion of KYSA-6 in generalized myasthenia gravis (搜索) (gMG). The company said the results support a single-dose, drug-free remission strategy and reinforce its rolling Biologics License Application (BLA) submission for SPS, which it expects to complete in the fourth quarter of 2026.
The readout arrives as two large pharmaceutical companies contend with safety setbacks in the same autoimmune CAR-T field. Novartis implemented a blanket hold on its CD19 (搜索) CAR-T candidate rapcabtagene autoleucel (rap-cel) across multiple autoimmune trials after three patient deaths from severe IEC-HS. Bristol Myers Squibb (搜索) voluntarily paused enrollment in autoimmune trials of its CD19-targeted zolacabtagene autoleucel (zola-cel) after observing transient and reversible inflammatory events.
One-year SPS data
As of a July 2026 database lock, 12-month follow-up data covered 26 patients with SPS who received a single dose of miv-cel in KYSA-8, a single-arm registrational Phase 2 trial enrolling adults with an inadequate response to at least one prior immunotherapy. The trial's primary endpoints are change from baseline in the timed 25-foot walk test (T25FW) at 16 weeks and the incidence and severity of adverse events. Secondary endpoints include the Modified Rankin Scale, Distribution-of-stiffness Index, Heightened Sensitivity Scale and Hauser Ambulation Index.
Median T25FW improvement from baseline was 46% at week 16 and 49% at month 12, with the month-12 result significant at p < 0.0001. Kyverna reported that 95% of patients who achieved a clinically meaningful improvement, defined as a greater than 20% reduction from baseline at the primary analysis, sustained that benefit at one year. More than one-third of patients completed the T25FW in under 5 seconds, a time the company described as comparable to healthy adults. Of the 12 patients who required a walking aid before treatment, 67% continued to need no assistance. Significant improvements in secondary endpoints remained consistent at 12 months, with p values between <0.0001 and 0.0003. Ninety-two percent of patients remained free of chronic immunotherapies for SPS.
"The results from KYSA-8 are compelling, particularly given the severe burden of SPS and the absence of approved therapies," said Amanda Piquet, M.D., FAAN, director of autoimmune neurology at the University of Colorado Anschutz School of Medicine, Céline Dion Foundation endowed chair and lead investigator of the KYSA-8 trial. "After a single dose of miv-cel, the sustained improvements observed in mobility, stiffness and other disease-specific measures, together with a well-tolerated profile, underscore its potential to deliver significant, long-lasting benefit to patients with SPS."
Kyverna CEO Warner Biddle said the durability data will strengthen the eventual label. "Ultimately, it will make our label stronger once we reach the commercialization stage," he told Fierce Biotech, adding that the one-year analysis "reinforces our package."
Safety profile and construct differences
Miv-cel continued to be well tolerated, with no high-grade cytokine release syndrome (CRS), no immune effector cell-associated neurotoxicity syndrome (ICANS) and no cases of immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) in one-year follow-up. Biddle said the drug has shown no high-grade CRS or ICANS and no IEC-HS events after use in more than 100 patients.
He attributed the profile to the construct and manufacturing approach. "We've got a unique construct with miv-cel. This is the only CD19 (搜索) CAR in the autoimmune space that's a CD28 co-stimulatory domain, fully human [CD19 binding domain], and has been designed for significantly improved safety profiles," Biddle said. Unlike rapid manufacturing technologies, miv-cel uses a conventional CAR-T production process, he added. Kyverna describes miv-cel as a fully human, autologous, CD19-targeting CAR T-cell therapy with CD28 co-stimulation, designed for deep B-cell depletion and produced using a validated manufacturing process.
gMG follow-up extends to 1.5 years
In the Phase 2 portion of KYSA-6, a single-arm, open-label, multicenter study, seven patients with moderate to severe gMG received one dose of miv-cel. All had failed prior immunosuppressant therapies, including FcRn and complement inhibitors. As of a June 2026 data cut-off, follow-up extended beyond one year, up to 1.5 years, in five patients, with one patient at 9 months and another at 6 months.
All seven patients (100%) achieved clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) at 24 weeks, with mean reductions of -8.3 and -11.7 points. Those two measures are the co-primary endpoints of the ongoing Phase 3 portion. Clinically meaningful improvements in MG-ADL, QMG and Myasthenia Gravis Composite scores were maintained through one year or longer in all five patients who reached that time point. Minimal symptom expression, defined as an MG-ADL score of 0 or 1, was maintained in 57% of patients as of last follow-up.
All seven patients remained free of immunotherapies for MG at 24 weeks, including nonsteroidal immunosuppressive therapies, high-dose steroids above 10 mg, and FcRn and complement inhibitors, with six of seven (86%) still off immunosuppressants at last follow-up. No high-grade CRS, ICANS or IEC-HS was reported.
The Phase 3 portion of KYSA-6 is a roughly 60-patient, global, open-label, randomized controlled trial with a crossover design evaluating miv-cel against standard of care. Co-primary endpoints are MG-ADL and QMG; secondary endpoints include MGC change from baseline at 24 weeks versus standard of care, the proportion of patients with at least a 3-point improvement in MG-ADL at 24 weeks versus standard of care, and the proportion with minimal symptom expression at 24 weeks versus standard of care. Enrollment is expected to complete in mid-2027.
Regulatory path and pipeline
Kyverna intends to include the one-year SPS data in its rolling BLA submission, with completion on track for the fourth quarter of 2026. The full data set is scheduled for presentation at MS Toronto, the joint ACTRIMS-ECTRIMS meeting, on October 21 to 23, 2026, in Toronto. Additional longer-term KYSA-6 Phase 2 data will be presented orally at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting on September 29, 2026, in Orlando, Florida.
Miv-cel holds three FDA Regenerative Medicine Advanced Therapy designations, in SPS, gMG and non-active secondary progressive multiple sclerosis (搜索). If approved, it would be the first CAR-T therapy for an autoimmune disease and the first approved therapy in SPS.
"There are currently no FDA-approved treatments for SPS," the company noted, describing current options as symptomatic treatments, off-label immunotherapies such as intravenous immunoglobulin, rituximab and plasmapheresis, and supportive care, with the majority of patients having inadequate or no response. Biddle said the ability to take most patients off chronic immunosuppressants and high-dose steroids is "resetting the conversation that we're having about this disease."
SPS is a rare, progressive neurologic autoimmune disease characterized by muscle stiffness and painful muscle spasms that affect mobility and gait. Up to 80% of patients lose mobility and require walking aid assistance or wheelchair use, and the disease has been associated with permanent disability and increased mortality risk. Most patients have antibodies to glutamic acid decarboxylase 65 (搜索) or the glycine receptor. An estimated 6,000 patients are diagnosed with SPS in the United States.
For gMG, a B-cell and antibody-mediated autoimmune neuromuscular disease causing muscle weakness and fatigue, an estimated 80,000 patients are diagnosed in the United States. Up to 20% of patients experience respiratory crisis at least once. Biddle said miv-cel offers the chance to reset the immune system with durable benefit from a single dose, compared with available chronic treatment options. He added that Kyverna is building a neuroimmunology portfolio, with gMG as the next indication and diseases such as progressive multiple sclerosis (搜索) to follow.