Kyverna’s CAR-T Gets RMAT Designation for Myasthenia Gravis
A patient with MG is also the first evaluated to reach 1 year of follow-up and has a continued durable immunomodulator-free response.
Srikanth Muppidi, MD
Credit: Stanford Medicine
The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) to Kyverna Therapeutics’ KYV-101 chimeric antigen receptor (CAR) T-cell therapy for the potential treatment of progressive myasthenia gravis (MG).1
"The RMAT designation underscores the attention and interest by the FDA in the development of potentially transforming therapies targeting a severe autoimmune disease such as myasthenia gravis," principal investigator Srikanth Muppidi, MD, a neuromuscular disorder specialist at Stanford Medicine in Palo Alto, California, said in a statement.1 "We are witnessing an era of profound changes in the approach to autoimmune conditions and ultimately, we hope this leads to a symptom-free state for patients."
KYV-101 is an autologous, fully human CD19-targeted CAR T-cell therapy. Kyverna has been expanding the use of KYV-101 into a number of B cell-driven autoimmune diseases after the CAR in KYV-101 was originally designed by the National Institutes of Health (NIH) for use in oncology.
"We are very happy with the constructive scientific rapport established between Kyverna and the FDA," Peter Maag, PhD, chief executive officer, Kyverna, added.1 "We believe the RMAT designation may ultimately add to our rigorous approach to KYV-101 development in the hope of benefitting the most deserving patients."
READ MORE: Kyverna’s CAR T Seems Feasible in Multiple Sclerosis
KYV-101 received clearance to be evaluated in patients with MG late last year, allowing Kyverna to initiate the ongoing phase 1/2 KYSA-6 trial (NCT06193889).2
Kyverna reported initial data on the use of KYV-101 in patients with MG and other autoimmune diseases from KYSA-6 and other trials at the European Alliance of Associations for Rheumatology (EULAR) European Congress of Rheumatology 2024, held June 12-15, in Vienna, Austria.3
The company reported data from 30 patients treated with KYV-101 for autoimmune disease indications as of May 30, 2024. 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-101.3
Notably, a patient with MG was the first to reach 1 year of follow-up and 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.3
"CAR T-cell therapies are rapidly establishing themselves as the new North star in the autoimmune disease treatment universe," Maag said in a statement about the new data.4 "We are seeing rising interests in unlocking the full potential of cell therapies in rheumatological and neurological B-cell driven autoimmune diseases."
