Kyverna Reports Sustained Clinical Benefit With miv-cel in Refractory RA

Kyverna Therapeutics has reported updated Phase 1 results from the investigator-initiated COMPARE trial (NCT06475495), presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress in London. The company’s CD19-directed CAR T-cell therapy, mivocabtagene autoleucel (miv-cel; KYV-101), demonstrated profound B-cell depletion, sustained autoantibody suppression, and durable clinical benefit in patients with anti-citrullinated protein antibody (ACPA)-positive, treatment-refractory rheumatoid arthritis (RA).

Immune Reset Through B-Cell Depletion

Miv-cel is an autologous CAR T-cell therapy incorporating CD28 co-stimulation that targets disease-driving B cells and promotes immune reconstitution. Investigators observed deep depletion of CD19-positive B cells and plasmablasts across blood and tissue compartments, followed by repopulation with predominantly naïve B-cell populations, a pattern consistent with immune reset.

Disease-associated autoantibodies, including ACPA and rheumatoid factor IgA and IgM, declined substantially and remained suppressed for up to 52 weeks while protective vaccine immunity was preserved. The findings suggest that a single infusion of miv-cel may alter the underlying autoimmune process rather than simply suppress disease activity.

Clinical Outcomes in Highly Refractory Patients

The Phase 1 portion of the open-label COMPARE study enrolled six patients with active ACPA-positive RA who had failed a median of 6.5 biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). Patients received a single infusion of 1×10⁸ miv-cel CAR T cells following lymphodepletion and were followed for up to 52 weeks.

The primary endpoint was safety and tolerability, with efficacy and biomarker assessments evaluated as secondary measures.

All six patients experienced meaningful reductions in disease activity, including fewer swollen and tender joints and reduced inflammation. By Week 36, 66.6% of patients achieved an ACR70 response, indicating substantial improvement in disease symptoms. Investigators also reported deep depletion of autoreactive B cells in peripheral blood and tissue sites, accompanied by sustained reductions in disease-associated autoantibodies.

Favorable Safety Profile

Miv-cel maintained a favorable safety profile consistent with previous experience across more than 100 treated patients. No cases of high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.

Researchers at Charité – University of Berlin highlighted the therapy’s ability to eliminate pathogenic B cells from key disease reservoirs, including bone marrow and inflamed joints. The return of predominantly naïve and transitional B-cell populations further supports the potential for durable immune reconstitution following treatment.

Next Steps: Head-to-Head Against Rituximab

The COMPARE trial has now advanced into Phase 2, which is fully enrolled. This portion of the study directly compares miv-cel with rituximab in patients with active ACPA-positive, treatment-refractory RA and moderate-to-high disease activity.

The study is expected to provide important evidence on whether CAR T-cell-mediated immune reset can deliver deeper and more durable disease control than the current anti-CD20 standard of care.

Broader Pipeline Context

Beyond RA, miv-cel is under evaluation in several B-cell-mediated autoimmune diseases, including lupus and multiple sclerosis. The single-infusion approach aims to provide durable disease control through deep B-cell depletion and immune reconstitution, potentially offering an alternative to chronic immunosuppressive treatment strategies.

Reference

Kyverna Therapeutics Highlights Updated Miv-cel Data at EULAR Demonstrating Substantial Reduction in Disease Activity in ACPA-Positive, Treatment Refractory Rheumatoid Arthritis | Kyverna Therapeutics