Miv-Cel Phase 2 Data Signal Manufacturing Readiness Pressure for CAR-T Makers

Kyverna Therapeutics' mivocabtagene autoleucel (miv-cel) posted a median 46% improvement in timed 25-foot walk at week 16 in a phase 2 single-arm registrational trial for stiff person syndrome (SPS), a rare autoimmune neurological disorder with no FDA-approved treatment. For autologous CAR-T manufacturers and CDMOs, a therapy advancing through a registrational pathway in an orphan indication with no approved comparator means GMP facility qualification, vein-to-vein logistics, and process validation timelines move from planning exercises to operational imperatives.

The trial enrolled 26 patients who had failed at least one prior immunotherapy. The 46% median improvement exceeded the 20% threshold regarded as clinically meaningful in this setting. Among 12 patients requiring walking assistance at baseline, 63% completed the 25-foot walk without assistance by week 16. Across primary and secondary endpoints including the modified Rankin Scale, Hauser Ambulation Index, Stiffness Index, and a hypersensitivity scale, 96% of participants showed improvement on at least one measure. No high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) events were reported.

Amanda Piquet, MD, FAAN, director of the Autoimmune Neurology Program at the University of Colorado and holder of the Celine Dion Foundation Endowed Chair in Autoimmune Neurology, presented findings at the 2026 American Academy of Neurology Annual Meeting in Chicago. Piquet characterized the safety profile as consistent with class expectations and noted that functional outcomes observed, including patients who relied on walkers at baseline ambulating independently by week 16, are not achievable with current off-label approaches such as intravenous immunoglobulin.

Piquet identified long-term durability as the key open question. The 16-week primary endpoint data reflect a follow-up of approximately 6.5 months at data cutoff; the full trial runs 12 months. For quality and manufacturing teams, that durability question carries direct implications for comparability studies, release testing specifications, and any post-approval commitments that a BLA submission would require under 21 CFR Part 211 and ICH Q10 quality system expectations.

Source: Data were presented at the 2026 AAN Annual Meeting (April 18-22, Chicago). Interview conducted by CGTLive's sister publication NeurologyLive on the conference floor.