Kyverna's CAR-T Therapy Shows Promise in Autoimmune Disease Trial

Kyverna Therapeutics has reported encouraging results from a small trial of its CAR T-cell therapy, KYV-101, in patients with generalized myasthenia gravis (gMG). The phase 2 data demonstrate significant improvements in disease outcomes, potentially positioning KYV-101 as a competitive player in the growing field of autoimmune treatments.

Trial Results and Comparisons

The phase 2 portion of Kyverna's registrational trial included six patients with moderate to severe gMG who had previously failed to respond to conventional immunosuppressant therapies. After a single dose of KYV-101, patients showed substantial improvements in key efficacy measures:

• An eight-point improvement on the MG-ADL scale was observed in three patients with 24 weeks of follow-up. This compares favorably to the 3.1- to 4.6-point reductions seen in trials of competing therapies such as argenx's Vyvgart and AstraZeneca's Ultomiris.

• A 7.7-point drop on the QMG scale, another measure of disease severity, outperformed the 2.8 to 6.2-point declines reported in rival trials.

Dr. Srikanth Muppidi of Stanford Medicine, while describing the data as "quite promising," cautioned that cross-trial comparisons should consider factors such as the higher disease burden in Kyverna's trial participants.

Safety Profile and Mechanism

KYV-101, a CD19-directed CAR-T therapy with CD28 co-stimulation, demonstrated a manageable safety profile:

• All six patients experienced cytokine release syndrome, a common side effect of CAR-T therapies, with two grade 2 cases and four grade 1 cases.

• No cases of immune-effector-cell-associated neurotoxicity syndrome were reported.

• Grade 3 and 4 cases of neutropenia were observed, linked to the lymphodepletion process.

Competitive Landscape and Future Outlook

Kyverna's results place KYV-101 in a competitive position within the evolving landscape of CAR-T therapies for autoimmune diseases:

• Other companies developing CAR-T therapies for gMG include Cartesian Therapeutics (with a BCMA-targeted approach), Cabaletta Bio, and Novartis (both pursuing CD19-directed therapies).

• Kyverna CEO Warner Biddle expressed increased confidence in the potential for phase 3 success, noting that the observed effects exceeded assumptions for the pivotal study's primary endpoint.

The company is now enrolling 60 participants in the phase 3 portion of the study, which will compare KYV-101 to the standard of care. As the trial progresses, Kyverna's therapy could potentially offer a new treatment option for patients with refractory gMG, addressing an significant unmet need in the management of this challenging autoimmune condition.