Kyverna Therapeutics has reported deep, sustained improvements in autoimmune disease patients who received a single dose of its CAR T-cell therapy KYV-101.
The data come from the phase 2 part of a trial Kyverna is running to support the registration of the cell therapy in generalized myasthenia gravis (gMG). As of the data cutoff, the biotech had results for six patients with moderate to severe gMG. The patients, who had gMG for an average of 5.3 years, had tried immunosuppressant therapies such as FcRns and complement inhibitors in the past without success.
Kyverna saw an eight-point improvement on the MG-ADL scale, which measures the impact of gMG on daily functions, in the three patients with 24 weeks of follow-up. The company compared the result to the 3.1- to 4.6-point reductions seen in trials of argenx’s Vyvgart and AstraZeneca’s Ultomiris, respectively.
The KYV-101 data also compare favorably to the results on Amgen’s Uplizna and Cartesian Therapeutics’ Descartes-08, both of which are in development in gMG. Both companies have seen 4.2-point changes on the scale. Descartes-08 is an mRNA CAR-T therapy. But, whereas KYV-101 is a CD19 treatment with CD28 co-stimulation, Cartesian’s asset engages BCMA.
MG-ADL is the primary efficacy endpoint in the phase 2 trial and one of two co-primary endpoints in the phase 3 part of the study. The other phase 3 primary endpoint is quantitative myasthenia gravis (QMG), another measure of disease severity. Kyverna saw a 7.7-point drop on QMG in the phase 2 trial, compared to declines of between 2.8 and 6.2 points in its rivals’ trials.
Stanford Medicine’s Srikanth Muppidi, M.D., commented on the efficacy data on a call Kyverna held to discuss the results with analysts. Muppidi said the data are “quite promising” but flagged factors that could have affected the cross-trial comparisons. Patients in the Kyverna trial had a significant disease burden that was higher than in some phase 3 studies published to date, Muppidi said.
Two of the three patients had minimal symptom expression by Week 24. Kyverna CEO Warner Biddle said on the call that all the other patients in the trial were trending toward minimal symptom expression.
On the safety front, all six patients had cytokine release syndrome, a common side effect of CAR-Ts. Two of the cases were grade 2 and the other four were grade 1, indicating relatively mild effects. No patients had immune-effector-cell-associated neurotoxicity syndrome, another common CAR-T side effect. There were grade 3 and 4 cases of low neutrophils, a type of white blood cell, linked to lymphodepletion.
Biddle said the data boost his confidence in chances of phase 3 success because the results exceeded the magnitude of effect assumed for the pivotal study’s primary endpoint. The biotech is enrolling 60 people in the phase 3 part of the study, which will compare KYV-101 to standard of care.
Kyverna is part of a group of companies developing CAR T-cell therapies in gMG. The group includes Cartesian’s BCMA program and CD19-directed CAR-T therapies that are in clinical development at Cabaletta Bio and Novartis.