Kyverna Therapeutics looks all the more likely to win the first FDA approval for a CAR-T therapy in an autoimmune disease after a registrational trial showed “highly statistically significant” benefits for the company’s mivocabtagene autoleucel (miv-cel) on its primary endpoint and all secondary endpoints, according to the company.
A single dose of miv-cel showed “truly remarkable” results in the phase 2 KYSA-8 trial in patients with stiff person syndrome (SPS) who had an inadequate response with non-approved treatment options, Amanda Piquet, M.D., director of autoimmune neurology from the University of Colorado Anshutz School of Medicine and lead investigator of the study, said during a conference call Dec. 15.
SPS is a rare, progressive neurological autoimmune disease in which muscle stiffness and spasms throughout the body cause up to 80% of patients to lose mobility, meaning they need walking aid or a wheelchair. The public became more familiar with the condition following Céline Dion’s diagnosis. For this disorder, which is estimated to affect about 1 to 2 people per million, there are currently no FDA-approved therapies. Instead, off-label immunotherapies, meds to address the symptoms, psychiatric therapy and other supportive care are offered to patients.
Miv-cel, formerly KYV-101, is an autologous CD19-targeted CAR-T cell therapy designed to eliminate CD19-positive B cells to reset the immune system. The one-time therapy’s CAR design includes a CD28 co-stimulatory module to enhance the therapeutic cells’ persistence and potency for a potentially more durable effect.
In the registrational KYSA-8 trial, miv-cel on average reduced the time that 26 patients took to finish a 25-foot walk test by 46% at Week 16 compared with baseline. The result’s p-value was 0.0002, suggesting it’s very unlikely that the improvement happened by chance. Among them, 81% of patients achieved a clinically meaningful reduction of at least 20%.
Further, the trial included secondary endpoints measuring patients’ degree of disability, muscle stiffness in various parts of the body, the triggers of muscle spasms and the combination of time and assistance used to complete the 25-foot walk test.
“It was important to include all of these measures in our trial to ensure a robust evaluation of miv-cel efficacy,” Kyverna’s chief medical and development officer, Naji Gehchan, said on Monday’s call.
While the detailed efficacy data from the secondary endpoints won’t be shared until a future medical conference, the p-value for every one of them was below 0.0001, which is highly statistically significant, according to Kyverna.
These are “unprecedented” results that doctors have never seen with existing off-label therapies, Piquet said.
Miv-cel also showed what Kyverna called a manageable safety profile. Ninety-two percent of patients developed cytokine release syndrome, but only at grade 1 or 2, and 12% experienced immune effector cell-associated neurotoxicity syndrome only at grade 1. Sixteen patients (62%) had grade 3 or 4 neutropenia, another known adverse event associated with CAR-T treatments.
Based on the data, Piquet suggested that miv-cel could be beneficial for patients even beyond the eligibility criteria of the current study.
“We know this disease to be progressive, so even patients that are stable right now in our clinical practice likely won't be in the future,” Piquet said. “Given the fact that these off-label treatments are often inadequate or the durability of response is not sustained […] these patients may be candidates for miv-cel in the future.”
With these data, Kyverna plans to file for FDA approval in the first half of 2026. The drug has received regenerative medicine advanced therapy and orphan drug designations in SPS, and Kyverna has had a “really strong and consistent dialogue with the FDA,” Kyverna CEO Warner Biddle said on Monday’s call.
The company plans to initially target about 2,000 to 2,500 patients treated with off-label immunotherapy, while the company put the total addressable market for miv-cel in the U.S. at about 5,500 patients, or 90% of all SPS patients diagnosed.
The company continues to “assess the opportunity to accelerate the development and the filing” for miv-cel, Biddle said in response to a question about whether Kyverna will seek a Commissioner’s National Priority Voucher, a recently launched pilot program by the FDA that aims to accelerate the review of drugs that align with certain U.S. national priorities. Monday, the FDA doled out a voucher to Johnson & Johnson based on that company's “potentially transformative“ trial result in relapsed/refractory multiple myeloma, agency Commissioner Marty Makary, M.D., said in a statement.
Analysts on Monday’s call also called the results “remarkable” or “stellar.” In a Dec. 15 note, Leerink Partners analysts called the readout a “best-case scenario” for Kyverna, as it comes ahead of the company’s guided timeline of an early 2026 report. The Bay Area biotech’s stock price jumped about 30% Monday morning as of publication time.
Patients in the KYSA-8 trial will be followed for a year. So far, 16 patients have had at least 24 weeks of follow-up. All patients remained free of immunotherapies as of the last follow-up.
“We believe this highlights miv-cel’s potential to provide unprecedented clinical benefit, while significantly reducing or eliminating chronic treatment burden,” the Leerink team wrote in their note.
CD19 CAR-Ts have been approved for various blood cancers. Enthusiasm around them for the treatment of autoimmune disorders was sparked by early clinical evidence in lupus.
While lupus has attracted a lot of interest, Kyverna picked SPS to be miv-cel’s initial indication so it can be the first CAR-T to enter the autoimmune field.
SPS is “our tip of the spear that will allow us to establish a base as the first autoimmune CAR company,” Biddle, who joined Kyverna from Gilead Sciences’ cell therapy outfit Kite Pharma, said in an interview with Fierce Biotech in January.
The company has also reported promising phase 2 results for miv-cel in generalized myasthenia gravis. Phase 1 lupus nephritis data are expected in 2026.