Kyverna’s CAR-T KYV-101 Shows Some Durable Responses in Autoimmune Disease, With One Relapse Reported

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One patient is considered disease-free at 1 year posttreatment, but another patient’s disease relapsed at 5 months.

Peter Maag, PhD, the chief executive officer of Kyverna

Peter Maag, PhD

Kyverna Therapeutics’ KYV-101, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for various autoimmune indications, has shown mixed efficacy results in newly reported data from the first set of patients treated.1 The data were presented at the European Alliance of Associations for Rheumatology (EULAR) European Congress of Rheumatology 2024, held June 12-15, in Vienna, Austria.

Kyverna reported that as of May 2024, 30 patients have been treated with KYV-101 for autoimmune disease indications. The data comes from multiple clinical trials and case reports covering 6 rheumatology indications and 9 neurology indications. Of these 30 patients, 30 achieved B-cell depletion and 29 experienced CAR-T expansion. Autoantibody reduction (or impact on IgG oligoclonal bands in patients with multiple sclerosis or reduced IgG4 levels in patients with IgG4-releated disease) was observed in 28 patients, with 6 patients showing this within less than 90 days of receiving the CAR-T. Similarly, disease impact, defined as a demonstration of reduced clinical and biological activity, was observed in 28 patients, with 6 patients showing disease impact within less than 90 days of treatment. Durable immunomodulator-free responses (DIFRs), with a durable response defined as no immunomodulator use for 3 or more preceding months at the time of the data cutoff, were achieved by 21 patients. Ten of these 21 patients achieved their DIFR within less than 90 days of receiving KYV-101.

Notably, the first patient to reach 1 year of follow-up, has maintained her DIFR as of the data cutoff. The patient, who was treated with KYV-101 for refractory myasthenia gravis, is now considered disease-free, with no adverse events (AEs) having occurred, and is not taking any background immunosuppressants or glucocorticoids. Her B-cells had repopulated as of 132 days of follow-up.

On the other hand, a different patient treated with KYV-101 for lupus nephritis experienced disease recurrence at 5 months posttreatment, despite having an initial disease response. Kyverna noted that the patient has a high BMI and was treated with a dose of 50 million CAR T-cells. According to Fierce Biotech, the relapse is only the second ever to be reported in a patient who received a CAR-T therapy for an autoimmune disease indication, with the first having occurred in clinical trial carried out at by an academic institution rather than a company.2 Fierce Biotech noted that Kyverna’s stock value dropped by approximately 34% in premarket trading on the Monday after the presentation was given, attributing the drop to the announcement of the new disease relapse. CGTLive® has reached out to Kyverna for comment on the relapse and is currently awaiting a reply.

In terms of safety, 25 of the 30 treated patients experienced cases of cytokine release syndrome (CRS) and 3 of the treated patients experienced cases of immune effector cell-associated neurotoxicity syndrome (ICANS).1 Although, none of the cases of CRS or ICANS were assessed as grade 3 or higher. Kyverna characterized the safety profile of KYV-101 in the 30 patients as “promising”.

"CAR T-cell therapies are rapidly establishing themselves as the new North star in the autoimmune disease treatment universe," Peter Maag, PhD, the chief executive officer of Kyverna, said in a June 7, 2024, statement regarding the then-upcoming data presentation at EULAR.1 "We are seeing rising interests in unlocking the full potential of cell therapies in rheumatological and neurological B-celldriven autoimmune diseases."

Notably, just last week, Kyverna received clearance of an additionalinvestigational new drug (IND) application from the FDA for KYV-101.4 The new IND allows Kyverna to evaluate the CAR-T for the treatment ofstiff-person syndrome (SPS) in a phase 2 clinical trial referred to as KYSA-8.

"CAR T-cell therapy has already shown preliminary but promising results in patients with SPS treated outside of the United States," Marinos Dalakas, MD, FAAN, professor of neurology, and director of the Neuromuscular Division at Thomas Jefferson University School of Medicine, said in a statement.4 "I find the KYSA-8 trial of extraordinary importance as a promising novel therapy for patients with SPS who do not respond to current therapies, with implications in providing potentially long-lasting benefits."

REFERENCES
1. Maag P. Anti-CD19 CAR T-cell therapy in rheumatologic autoimmune diseases and beyond. Presented at:EULAR European Congress of Rheumatology 2024, held June 12-15, in Vienna, Austria.
2. Kyverna's CAR-T relapse in lupus dents autoimmune hopes amid biotech gold rush. News article. Helen Floersh, Fierce Biotech. June 17, 2024. Accessed June 24, 2024. https://www.fiercebiotech.com/biotech/kyverna-reports-relapse-early-stage-car-t-lupus-trial
3. Kyverna Therapeutics to present data on 50 patient experience at symposium at EULAR 2024. News release. Kyverna Therapeutics, Inc. June 7, 2024. Accessed June 24, 2024. https://ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-present-data-50-patient-experience-0
4. Kyverna's KYV-101 Receives U.S. FDA IND Clearance for Treatment of Patients With Treatment-Refractory Stiff-Person Syndrome in the KYSA-8 Phase 2 Trial. News release. Kyverna Therapeutics. June 20, 2024. Accessed June 24, 2024. https://ir.kyvernatx.com/news-releases/news-release-details/kyvernas-kyv-101-receives-us-fda-ind-clearance-treatment
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