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Prior to this, the FDA granted regenerative medicine advanced therapy designation to the cell therapy for refractory stiff-person syndrome.
Srikanth Muppidi, MD
(Credit: Stanford Medicine)
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 FDA cleared the company’s investigational new drug (IND) application for KYV-101 to assess the efficacy and safety in a phase 2 study, dubbed KYSA-6, in patients with MG.2 Although Kyverna did not include much details on the design of the trial in its former release but that they noted that it expands on the current pipeline, which includes the ongoing US-based phase 1 KYSA-1 study and the phase 1/2 KYSA-3 trial in Germany, a trial of patients with active lupus nephritis.
"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
READ MORE: FDA Clears IND for CAR-T Cell Therapy Equecabtagene Autoleucel in Multiple Sclerosis
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.
