As two Big Pharma players in the autoimmune CAR-T space face unexpected safety setbacks, Kyverna Therapeutics is reporting long-term clinical data that showcase sustained efficacy alongside an unblemished safety profile for its potential first-in-class candidate, miv-cel.
A single dose of miv-cel (mivocabtagene autoleucel) showed durable clinical benefit out to 12 months in a registrational trial for stiff person syndrome (SPS) and up to a year and a half in the phase 2 portion of a study for generalized myasthenia gravis (gMG), according to data released Thursday.
With zero cases of high-grade cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), Kyverna plans to add the updated one-year data to its FDA rolling submission for miv-cel in SPS, keeping the biotech on track to complete its application in the fourth quarter.
The latest results showcase durable remission of miv-cel that “allows these patients to have a drug-free, disease-free remission and do so with a well-tolerated safety profile,” Kyverna CEO Warner Biddle told Fierce in an interview.
In the Kysa-8 trial, 26 patients with SPS who received miv-cel showed a median 49% improvement on the timed 25-foot walk test (T25FW) after 12 months versus baseline. The sustained efficacy marked a slight improvement from the 46% recorded at week 16, which already translated into a statistically significant win on the trial’s primary endpoint.
All but one patient who had previously achieved a clinically meaningful improvement— defined as at least a 20% reduction from baseline—at the 16-week primary analysis sustained that level of benefit at at the one-year mark.
Over a third of patients completed T25FW in less than 5 seconds, comparable to healthy adults. SPS is believed to be an autoimmune condition, in which antibodies mistakenly attack large molecules that are key for neurotransmission. The disease is characterized by muscle stiffness and painful muscle spasms, causing patients to lose mobility.
Consistent with the 16-week data, eight of 12 patients (67%) who had required a walking aid prior to treatment continued to no longer need assistance at one year.
“Stiff person syndrome is a progressive, highly debilitating disease where universally patients become more debilitated over time,” Biddle said.
“Everything that’s being used at this point is off label,” the CEO pointed out. “Nothing addresses the underlying cause of the disease or prevents the disease from progressing. The ability for us to have this sustained effect across a vast majority of the patients is the key message here.”
So far, 92% of patients remained free of chronic immunotherapies for SPS. One patient who enjoyed a clinically meaningful response to miv-cel at the primary analysis later chose to go on intravenous immunoglobulin (IVIG) in the hopes of improving their symptoms further. One other patient didn’t respond and restarted immunotherapy, according to Biddle.
“The fact that we’ve got a vast majority of patients off not just IVIG but chronic immunosuppressants and high doses of steroids again is resetting the conversation that we’re having about this disease and the potential to change the paradigm of how these patients should be managed,” Biddle said.
“The results from KYSA-8 are compelling, particularly given the severe burden of SPS and the absence of approved therapies,” Amanda Piquet, M.D., from the University of Colorado, Céline Dion Foundation endowed chair, and lead investigator of the Kysa-8 trial, said in a statement.
“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,” Piquet added.
While the 16-week data is forming the core of Kyverna’s FDA rolling submission for miv-cel in SPS, the one-year analysis “reinforces our package,” Biddle said. “Ultimately, it will make our label stronger once we reach the commercialization stage.”
If approved, CD19-targeted miv-cel will be the first CAR-T therapy for an autoimmune disease.
The recent momentum around autoimmune CAR-T therapies faced its first major test late last month when industry heavyweights Novartis and Bristol Myers Squibb encountered potentially serious safety signals.
Novartis implemented a blanket hold for its CD19 CAR-T candidate, rapcabtagene autoleucel (rap-cel), across multiple autoimmune clinical trials following three patient deaths caused by severe IEC-HS. Around the same time, BMS voluntarily paused enrollment for its own autoimmune trials testing a CD19-targeted CAR-T, zolacabtagene autoleucel (zola-cel), after observing “transient and reversible inflammatory events.”
Analysts quickly pointed to both companies’ use of rapid manufacturing platforms as a potential trigger, speculating their methods could yield hyper-potent T cells prone to explosive cell expansion that may be dangerous to non-oncology patients.
Kyverna’s Biddle argued that miv-cel’s design and manufacturing process insulate it from similar toxicities.
“We’ve got a unique construct with miv-cel. This is the only CD19 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, pointing to how the drug has seen no high-grade CRS or ICANs or any IEC-HS events after being used in over 100 patients.
Unlike those rapid manufacturing technologies, miv-cel uses a well-validated conventional CAR-T production process, he added.
In addition to the SPS data, Kyverna on Thursday also provided an update for miv-cel’s Kysa-6 trial in gMG.
As the company previously disclosed, all seven patients enrolled in the phase 2 portion achieved clinically meaningful improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) at 24 weeks. As of data cut-off in June 2026, all five patients who had follow-up of at least one year sustained clinically meaningful improvements, Kyverna explained this morning.
Minimal symptom expression, defined as an MG-ADL score of 0 or 1, was maintained in 57% of patients as of last follow-up.
Before the latest long-term readout, Kyverna had already started enrollment into the phase 3 portion of the Kysa-6 study after the FDA blessed the company to truncate the phase 2 test. The trial is on track to finish enrollment in mid-2027, according to Biddle.
Compared with available chronic treatment options for gMG, miv-cel provides an opportunity to reset the immune system with durable clinical benefit in a single-dose treatment, Biddle said.
“We’re building a neuroimmunology portfolio,” Biddle said. “We’re looking to generalized myasthenia gravis as the next indication, and then other diseases like progressive [multiple sclerosis]. We think all of these steps allow us to continue to build our company in a very logical sequence to continue address larger patient populations over time.”