The autologous, fully human CD19 chimeric antigen receptor T-cell product, KYV-101, is being studied for the treatment of patients with progressive myasthenia gravis.
Updated on August 12, 2024 at 5pm.
The FDA has granted a regenerative medicine advanced therapy (RMAT) designation for KYV-101 (Kyverna Therapeutics, Inc.) for the treatment of patients with progressive myasthenia gravis (MG), an autoimmune disorder associated with muscle weakness in tissues throughout the body. The disorder can potentially manifest into partial paralysis of eye movements, problems chewing and swallowing, respiratory complications, speech difficulties, and musculoskeletal weakness.1
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Trial Name: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, in Subjects With Refractory Generalized Myasthenia Gravis
ClinicalTrials.gov ID: NCT06193889
Sponsor: Kyverna Therapeutics
Completion Date (Estimated): May 2027
Patients who have MG develop antibodies that may lead to an immunological attack on critical signaling proteins at the junction that resides between nerve and muscle cells, therefore, hindering the nerves’ ability to properly communicate with the muscles. The symptoms of MG can be transient, and in early stages, can remit spontaneously; however, as the disease progresses, disease exacerbations can last for months and symptom-free periods are less frequent. In approximately 80% of patients,, disease symptoms reach maximum levels within 2 to 3 years, and up to 20% of patients experience respiratory crisis at least once.1
KYV-101 is an autologous, fully human anti-CD19 chimeric antigen receptor (CAR) T-cell product candidate. The therapy is currently being investigated in the phase 2 clinical trial KYSA-6 (NCT06193889) for the treatment of adults with refractory generalized MG. Following clearance for an investigational new drug application, KYV-101 was granted a fast track designation by the FDA in December 2023 for refractory MG.1-3
"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 MG," said principal study investigator Srikanth Muppidi, MD, neuromuscular disorder specialist at Stanford Medicine in Palo Alto, CA, in a news release. "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."1
The open-label, multicenter phase 2 trial KYSA-6 (NCT06193889)—which was announced November 2023—is currently evaluating the safety, tolerability, and efficacy of KYV-101 as a treatment for patients with refractory generalized MG. Patients will receive the investigational therapy with a standard lymphodepletion conditioning regimen, cyclophosphamide (Cytoxan; Amneal Pharmaceuticals) or fludarabine (Fludara; Amneal Pharmaceuticals).3,4
The primary outcome measures include the safety and tolerability of KYV-101 (measured by the incidence of adverse events and laboratory abnormalities) which will be assessed up to 24 months, as well as the efficacy (measured by the MG Activities of Daily Living [MG-ADL] total score) which will be measured at 24 weeks. Additionally, secondary outcome measured include efficacy of KYV-101 via quantitative MG score and MG composite score (measured at 12, 24, and 52 weeks); disease-related antibodies via levels of anti-acetylcholine, anti-muscle-specific tyrosine kinase antibodies, and lipoprotein-related protein 4 antibodies (measured up to 2 years); pharmacokinetics via CAR-positive T cell counts, pharmacodynamics via B cell counts, pharmacodynamics via systemic cytokine concentrations, and immunogenicity (measured up to 2 years).3
Further, KYV-101 is under investigation in phase 1/2 and phase 2 clinical trials to assess efficacy in rheumatology and neurology. These include a phase 1/2 trial for systemic sclerosis, 2 ongoing multicenter, open-label phase 1/2 trials in the US and Germany for patients with lupus nephritis, as well as phase 2 trials for stiff person syndrome, multiple sclerosis, and MG.1
"We are very happy with the constructive scientific rapport established between [KYV-101] and the FDA," said Peter Maag, PhD, chief executive officer at Kyverna, in the news release. "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."1
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