Kyverna’s CAR T-Cell Therapy Expands Autoimmune Investigations Into Myasthenia Gravis

This article was first published by CGTLive^®. This version has been lightly edited.

The FDA has granted investigational new drug (IND) clearance for an open-label phase 2 trial of Kyverna Therapeutics’ KYV-101 chimeric antigen receptor (CAR) T-cell therapy in 10 patients with myasthenia gravis.¹

"We have seen firsthand the transformative effects of KYV-101 in MG patients treated with the investigational therapy in our clinic," Prof. Dr. med. Aiden Haghikia, director, Department of Neurology, medical faculty, Otto-von-Guericke University, Magdeburg, Germany, said in a statement.¹ "I welcome the FDA's decision and look forward to more clinical data to further our knowledge about CAR T-cell therapy in patients with severe neurological autoimmune diseases."

KYV-101 will be evaluated for safety and tolerability in the new indication in the KYSA-6 trial, and is being evaluated in patients with lupus nephritis in the phase 1 KYSA-1 trial (NCT05938725) in the United States and the phase 1/2 KYSA-3 clinical trial in Germany. For patients with diffuse cutaneous systemic sclerosis (scleroderma), KYV-101 is being assessed in the phase 1/2 KYSA-5 trial in the United States.

"We are grateful that the FDA's decision to clear the IND for our phase 2 KYSA-6 trial will allow Kyverna to offer this potentially paradigm-shifting investigational treatment to patients who may benefit from a deep B-cell depletion and possibly durable reset of their immune system," Peter Maag, PhD, CEO, Kyverna, said in the statement.¹

KYV-101 is an autologous fully human CD19 CAR T cell designed to treat B-cell–driven autoimmune diseases; it was in part designed by the National Institutes of Health for oncological indications. Kyverna plans to explore the use of KYV-101 in other autoimmune diseases. The company stated that it had also obtained clearance of 2 additional INDs for investigator-initiated trials of KYV-101 in the United States.

The IND clearance for Kyverna’s scleroderma program was granted in October 2023.² In September, the company announced that the first patient with lupus nephritis had been treated in the United States and the therapy had been well tolerated with 28 days of follow-up.³ The patient did not experience any immune effector cell–associated neurotoxicity syndrome. The US trial is seeking to recruit 9 to 12 patients with lupus nephritis across several clinical sites.

"We welcome Kyverna's enthusiasm and interest to push forward with their CAR T approach in scleroderma patients with the KYSA-5 trial," Luke Evnin, PhD, chairman of the Scleroderma Research Foundation, said in a statement.² "We await the results with optimism that CAR T–driven B-cell ablation may ultimately deliver efficacy with adequate safety for a broader range of our patients than immune-ablative chemotherapy alone."

References

1. Kyverna Therapeutics announces FDA clearance of phase 2 IND for KYV-101, a fully human CD19 CAR T-cell therapy to treat myasthenia gravis. News release. Kyverna Therapeutics. November 13, 2023. Accessed November 13, 2023. https://tinyurl.com/4mdkrt5n

2. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat scleroderma. News release. Kyverna Therapeutics. October 11, 2023. Accessed November 13, 2023. https://tinyurl.com/4zc4acma

3. Kyverna Therapeutics announces achievement of 28-day post-infusion milestone for first U.S. patient dosed in phase 1 clinical trial of CD19 CAR t-cell therapy for lupus nephritis. News release. Kyverna Therapeutics. September 13, 2023. Accessed November 13, 2023. https://tinyurl.com/5hap92xy