Kyverna miv-cel shows durable benefit in progressive MS at two years
Kyverna Therapeutics has presented updated clinical data from a Stanford University-led Phase 1 investigator-initiated trial of miv-cel (mivocabtagene autoleucel, KYV-101) in progressive multiple sclerosis, reporting durable improvements in disability scores out to more than two years in the longest-treated patient. The data were disclosed in an oral presentation at MS Toronto 2026, the joint ACTRIMS-ECTRIMS meeting, on 23 October.
Six patients received a single infusion of miv-cel at two dose levels, 33 million or 100 million CAR T-cells, following a bendamustine lymphodepleting conditioning regimen. All five patients with evaluable data showed stable or improved scores on the expanded disability status scale at last follow-up, with four of five sustaining that benefit beyond one year without the need for further chronic immunotherapy. The first patient treated has maintained clinical benefit for more than two years.
Biological activity and safety
Biological findings supported the therapy's proposed mechanism. CAR T-cell expansion was detected in peripheral blood within the first two weeks, and, critically, the cells penetrated the cerebrospinal fluid, a key challenge for CNS-directed therapies. Complete depletion of CD19-positive B cells was achieved in all patients, followed by repopulation of naive B cells from month three onwards, consistent with what the company describes as an immune reset. Biomarker data including CSF oligoclonal bands and kappa free light chain showed continued favourable immunological changes at one year.
The safety profile was notable for the absence of high-grade cytokine release syndrome and no reported cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or immune effector cell-associated haematophagocytic lymphohistiocytosis-like syndrome (IEC-HS), adverse events that have complicated other CAR T programmes, particularly in haematological oncology settings.
Jeffrey Dunn, clinical professor and chief of neuroimmunology at Stanford University, said the results provide "an important proof of concept" that miv-cel may offer a novel approach to progressive MS, while emphasising that confirmation in larger controlled trials is required.
Regulatory position and competitive landscape
Kyverna received an FDA Regenerative Medicine Advanced Therapy (RMAT) designation for miv-cel in non-active secondary progressive MS, adding to existing RMAT designations in stiff person syndrome and generalised myasthenia gravis. The designation provides more intensive FDA guidance during development. The company said it expects to outline a development strategy for progressive MS by early 2027.
The broader CAR T-cell space in autoimmune disease is attracting significant attention. Several academic groups and commercial sponsors, including Bristol Myers Squibb through its acquisition of Agenus assets, as well as Cartesian Therapeutics with its BCMA-targeting RNA CAR T programme in MS, are pursuing cell-based immune reset approaches. Progressive MS in particular remains a high unmet-need population: current approved disease-modifying therapies are largely ineffective in non-relapsing forms of the disease, where neurodegeneration proceeds independently of acute inflammatory activity.
Kyverna's single-dose positioning, if confirmed in controlled trials, would distinguish miv-cel from the chronic dosing required by standard-of-care agents. The company has also completed a registrational trial in stiff person syndrome and is running an ongoing registrational study in generalised myasthenia gravis, providing a broader commercial platform should regulatory submissions succeed. Investors and clinicians will look to the 2027 development strategy update for clarity on trial design, patient selection criteria and anticipated regulatory timelines for the progressive MS indication.