Kyverna's CAR-T relapse in lupus dents autoimmune hopes amid biotech gold rush

The “remarkable” success of chimeric antigen receptor T-cell therapy (CAR-T) in lupus has led to a gold rush as cell therapy companies shift their focus from oncology to immunology. But a new relapse in a clinical trial may dim the strategy’s glow, at least in the eyes of investors. 

A patient with lupus nephritis in a phase 1/2 clinical trial of Kyverna Therapeutics’ CAR-T therapeutic for autoimmune disease, KYV-101, has relapsed after five months despite initially responding, the company disclosed June 14 in a presentation of interim data on 50 subjects given at the EULAR European Congress of Rheumatology 2024 Industry Symposia. 

Kyverna's stock fell about 34% on the news, from $14.44 to $9.53, in premarket trading Monday. The relapse is the second one reported for an autoimmune CAR-T therapy. One patient with an autoimmune disease relapsed after treatment in a separate academic trial run by Georg Schett, M.D., whose proof-of-concept studies in patients with lupus kicked off industry excitement about cell therapy’s potential in immunology. Schett is a member of Kyverna’s scientific advisory board.

The results might bode well for a redosable CAR-T therapy like the one currently in development by Cartesian, Uy Ear, vice president of Mizuho, wrote in a June 14 note. While Kyverna’s treatment is based on DNA, Cartesian’s DESCARTES-08 is based on mRNA, so it doesn’t integrate into the genome of T cells. This means patients can be treated with it more than once without the safety risks presented by redosing DNA-based CAR-T therapies. 

“We believe these emerging [autoimmune CAR-T] data point to the need for redosing and a safer cell therapy option,” Ear wrote. “Descartes-08 confers distinct advantages—particularly on safety and for redosing, which we believe all CAR-Ts will require.”

Kyverna's full presentation showed that among the first 30 patients to receive the drug, three experienced immune effector cell-associated neurotoxicity syndrome, or ICANS, a potentially dangerous side effect of CAR-T, though none of the reactions were severe. Twenty-six patients had some degree of cytokine release syndrome, a common side effect of CAR-T therapy. 

On the other hand, the data also showed that CAR-T cells expanded in all but one of the same group, and the treatment depleted B cells in all of them. So far, 22 patients have seen long-term reductions in autoreactive antibodies or other disease-associated biomarkers; six have had reductions for up to 90 days, and two did not have any reduction, the data showed. 

As for the need for immune-modulating drugs, 11 of the 30 patients have gone without them long-term and 10 for up to 90 days. Nine of the patients did not have a durable response without drugs, the presentation showed. 

Kyverna’s first autoimmune patient to receive the treatment has been disease-free for a year with neither adverse effects nor the need for additional drugs. The person’s B cells repopulated by Day 132, according to the presentation.