Iaso Bio's BCMA CAR-T Therapy Ixazomib Injection Demonstrates Durable Efficacy and Favorable Safety in Refractory Myasthenia Gravis, Published in EMBO Molecular Medicine

Nanjing, Shanghai, and San Jose, CaliforniaFebruary 28, 2024/PR Newswire/ --On February 26, 2024, the international authoritative academic journal "EMBO Molecular Medicine" officially published the clinical research paper on IASO Bio's fully human BCMA-targeted chimeric antigen receptor autologous T (BCMA CAR-T) cell injection (Idecabtagene Vicleucel Injection, R&D code CT103A) for the treatment of two subjects with refractory myasthenia gravis (Myasthenia Gravis, MG) — B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.`, preliminarily demonstrating the good tolerability, safety, and durable clinical efficacy of BCMA CAR-T therapy in the treatment of MG.`

MG is an autoimmune disease characterized by acquired neuromuscular junction (NMJ) transmission dysfunction mediated by autoantibodies. The acetylcholine receptor (AChR) antibody is the most common pathogenic antibody; in addition, antibodies targeting other components of the postsynaptic membrane, including muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and ryanodine receptor (RyR), have been successively discovered to be involved in MG pathogenesis. Currently, the main treatments for MG include cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The primary causes of death in patients include respiratory failure and pulmonary infections.

This study is an investigator-initiated, open-label exploratory clinical trial (NCT04561557) evaluating the safety and efficacy of infusion of Icaritin Cell Injection in treating relapsed/refractory antibody-mediated idiopathic inflammatory neurological diseases. The study is conducted by Professor Wang Wei's team from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

The study enrolled two subjects with refractory MG. One subject was a 33-year-old female who was positive for AChR-IgG and Titin-IgG. She had undergone thymectomy 21 months prior to enrollment and had not achieved clinical remission despite treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and targeted CD20 monoclonal antibody therapy. The other subject was a 60-year-old female who was positive for MuSK-IgG4, with a 20-year history of the disease, and had previously received various ineffective treatments, including steroids, immunosuppressants, and targeted CD20 monoclonal antibodies. The two subjects were treated with 1.01×10⁶CAR-T/Kg and 0.96×10⁶Single infusion treatment with IASO Bio's CAR-T/Kg Ixazomib Injection.

Safety: Among the 2 subjects, only 1 subject experienced Grade 1 Cytokine Release Syndrome (CRS), and no Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurred. The ≥Grade 3 cytopenia recovered within 4 weeks after infusion. Compared with the safety profile in the multiple myeloma indication study, no new safety risks were identified, and the safety was better.

Effectiveness: Clinical symptoms of 2 subjects continued to improve for over 18 months. Significant improvements in limb strength and vital capacity were observed starting from 3 months after the infusion of Icaritinib injection. Myasthenia Gravis-Activities of Daily Living score (MG-ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis-Quality of Life score (MG-QOL), and modified Rankin Scale score (mRS) showed continuous improvement. During the follow-up period, apart from low-dose Neostigmine (90mg/day and 60mg/day respectively), no other immunomodulatory treatments were combined.

PK/PD: After infusion, Idecabtagene Vicleucel showed good expansion in the subjects but with a short duration. The anti-AChR and anti-Titin antibodies, as well as anti-MuSK antibodies in two subjects, rapidly decreased after infusion and remained at very low levels for a long time. B cells and plasma cells in both subjects dropped to undetectable levels within two months after infusion and then gradually recovered. B cells in both subjects returned to normal levels 18 months after infusion, with approximately 80% being naive B cells, while plasma cells remained at low levels. These results suggest that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells predominantly with a naive phenotype and the sustained depletion of plasma cells.

The principal investigator of this study,Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated："Myasthenia gravis has a long course, is difficult to cure, and prone to relapse. Although current traditional drug treatments can improve myasthenic symptoms to some extent, they are inadequate in terms of disease control and long-term safety. Patients have an urgent need for better clinical outcomes and treatment options. In our current IIT study, we are pleased to see that BCMA CAR-T cell therapy can halt the progression of MG and shows signs of reversing the disease, which is expected to change the treatment landscape for MG and bring hope of a cure to patients."

In addition to the research findings published this time, IASO Bio and the research team are continuing to explore the safety and efficacy of Equecabtagene Autoleucel Injection in treating other antibody-mediated autoimmune diseases, including Neuromyelitis Optica Spectrum Disorders (NMOSD), Immune-Mediated Necrotizing Myopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with the aim of transforming the treatment landscape for autoimmune diseases.