Prior to this, the FDA granted regenerative medicine advanced therapy designation to the cell therapy for refractory stiff-person syndrome.
According to a new announcement, the FDA has granted regenerative medicine advanced therapy (RMAT) to Kyverna Therapeutics’ autologous, fully human CD19 chimeric antigen receptor (CAR) T-cell product candidate KYV-101 for the treatment of patients with progressive myasthenia gravis (MG).1 KYV-101 is designed to target, recognize, and remove CD19, a specific protein expressed on the surface of B cells in various autoimmune disorders.
"The resetting of the patient's immune system has the potential to rewrite the book on neurological autoimmune disorders. While patient's well-being remains of utmost importance, we are grateful to the ones entering the clinical trial and contribute to advance our knowledge on what CAR T-cell therapy can do in a non-oncological setting," principal investigator Srikanth Muppidi, MD, a neuromuscular disorder specialist at Stanford Medicine, told NeurologyLive®.
In November 2023, the
"We are eager to commence enrollment in our MG KYSA-6 trial and engage in discussing the clinical evidence with all stakeholders involved," Peter Maag, PhD, chief executive officer at Kyverna, said to NeurologyLive.
CAR T cells have been seen as a versatile new class of effective, molecularly precise therapy. In addition to ongoing trials in lupus nephritis, the company noted in a prior release that it plans to assess KYV-101 in trials of systemic sclerosis and multiple sclerosis. The CAR in KYV-101 was designed by the National Institutes of Health to improve tolerability and was tested in a phase 1 trial (NCT02659943) in oncology with results published in Nature in 2020.3
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The first-in-human study featured 20 patients with B cell lymphoma with the primary objective of assessing safety and feasibility and secondary objectives of blood levels, ant-lymphoma activity, second infusions, and immunogenicity. KYV-101, known as just a Hu19-CD828Z T cell therapy at the time, met all study objectives. Treated patients demonstrated lower levels of cytokines than those who received FMC63-28Z T cells, which investigators noted could have explained the lower level of neurologic toxicity associated with the agent.
In September 2023, the company announced positive safety findings from a 28-day post infusion observation period in its phase 1 study assessing KYV-101 in patients with refractory lupus nephritis. In the open-label, dose-escalation, multicenter study, the Kyverna reported that the agent was well tolerated, with no cases of immune effector cell-associated neurotoxicity syndrome in a single patient treated with the agent.4
CAR T cell therapies, which have been successful in areas of cancer, are gaining more ground in the neurology field. In July 2023, data from the phase 1b/2 MG-001 trial (NCT04146051) published in Lancet Neurology was among the first to assess such therapy in patients with MG. Led by James F. Howard, MD, the study assessed Descartes-08, an autologous anti-B cell maturation antigen (BCMA) rCAR T therapy in adults with generalized MG who had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or higher.5
Comprised of 16 patients, the study showed that Descartes-08 was safe and well tolerated, with no dose-limiting toxicity, cytokine release syndrome, or neurotoxicity observed. Infusions with the agent were followed by clinically meaningful decreases on MG severity scales at up to 9 months of follow-up, although the study authors noted that further investigation is needed to validate efficacy benefits.
