Kyverna's CAR-T relapse in lupus hampers autoimmune hopes during biotech surge

Kyverna Therapeutics has been investigating the application of chimeric antigen receptor T-cell (CAR-T) therapy in treating lupus, an autoimmune disease. This approach, originally successful in oncology, has recently gained attention in immunology. However, a recent relapse in a clinical trial has raised concerns among investors about the reliability of this strategy.

In a Phase 1/2 clinical trial involving Kyverna’s CAR-T therapy for lupus nephritis, KYV-101, a patient who initially responded to the treatment relapsed after five months. This update was shared on June 14 during the EULAR European Congress of Rheumatology 2024 Industry Symposia. Following the announcement, Kyverna's stock plummeted by approximately 34%, from $14.44 to $9.53.

This relapse marks the second instance of an autoimmune disease patient relapsing following CAR-T therapy. Previously, another patient in a separate academic trial led by Dr. Georg Schett, a key figure in the cell therapy field and a member of Kyverna’s scientific advisory board, experienced a relapse. Schett’s initial studies had fueled optimism about the potential of CAR-T therapy for autoimmune conditions.

In light of these developments, there is growing interest in developing redosable CAR-T therapies. Cartesian Therapeutics, for example, is working on DESCARTES-08, an mRNA-based CAR-T therapy. Unlike DNA-based treatments like Kyverna’s, mRNA-based therapies do not integrate into the genome of T cells, allowing for multiple treatments without the associated safety risks. Uy Ear, vice president of Mizuho, emphasized the advantages of Cartesian's approach, particularly regarding safety and the potential necessity for redosing.

Kyverna’s interim data from the trial included some mixed results. Among the first 30 patients treated, three experienced immune effector cell-associated neurotoxicity syndrome (ICANS), a known side effect of CAR-T therapy, though none were severe. Additionally, 26 patients experienced cytokine release syndrome, another common side effect. Despite these issues, CAR-T cells expanded in all but one patient, and B cells were depleted in all. Furthermore, 22 patients showed long-term reductions in autoreactive antibodies or other disease biomarkers, with six maintaining these reductions for up to 90 days. However, two patients did not show any reduction.

Regarding the dependency on immune-modulating drugs, 11 of the 30 patients were able to go without them long-term, while 10 managed without them for up to 90 days. Nevertheless, nine patients did not have a sustained response without these drugs.

Notably, Kyverna's first autoimmune patient to receive the treatment has been disease-free for a year without adverse effects or the need for additional medication. The patient’s B cells repopulated by Day 132, indicating a successful response to the therapy.

In conclusion, while CAR-T therapy shows promise in treating autoimmune diseases such as lupus, recent setbacks highlight the need for further research and development. The potential for redosable, safer therapies like Cartesian’s DESCARTES-08 could play a crucial role in the future of CAR-T treatments in immunology.