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Promising Clinical Results on the World’s First Use of BCMA CAR-T to Treat Immune Mediated Necrotizing Myopathy (IMNM) Published on the Proceedings of the National Academy of Sciences (PNAS)

2024.02.01 | IASO,IASO Bio,IASO Biotherapeutics,IASO Biopharma,CT103A, CAR-T, cell therapy,dual-targeted CAR-T

On Jan. 30, 2024, PNAS published the research paper titled "Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR T-cell therapy." The paper analyzed results using the fully human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR)-antologous T cell (BCMA CAR-T) injection (Equecabtagene Autoleucel injection, R&D code: CT103A) for the treatment of IMNM, which showed durable pathogenic antibody clearance, and potentially persistent clinical efficacy with good tolerability and safety. This study provides a potentially new therapeutic option for antibody-mediated autoimmune disorders.

IMNM is an autoimmune-mediated skeletal muscle disorder belonging to an idiopathic inflammatory disease. IMNM mediated by human anti-signal recognition particle (SRP) antibody, an IMNM-specific autoantibody, is mainly characterized by symmetrical weakness of limb proximal muscles, prominent dysphagia, and significantly elevated serum creatine kinase, with features of acute onset, severe conditions, and rapid progression. Traditional pharmacological approaches have varying and often limited effects.

This study is an investigator-initiated, open-label, exploratory clinical study to evaluate the safety and efficacy of infusion of Equecabtagene Autoleucel in the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory diseases of the nervous system (NCT04561557).  The investigator team is led by Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

A 25-year-old male patient with a 7-year history of SRP antibody-positive refractory IMNM was enrolled in this study. The patient had been subject to repeated relapses and persistent injuries even after receiving multiple prior therapies including steroids, calcineurin inhibitors, folic acid antagonists, CD20 monoclonal antibodies, interleukin-6 (IL-6) receptor antagonists, inosine monophosphate dehydrogenase (IMPDH) inhibitors, alkylating agents, plasmapheresis, intravenous immunoglobulin injection, and mesenchymal stem cell infusion. Before enrollment, the patient was still paralyzed and bedridden. He was not able to lift his arms overhead and his serum creatine kinase was up to 4806 IU/L (Normal range ≤ 190 U/L) even under regular combination therapies with steroids, IL-6 receptor antagonists, folic acid antagonists, and intravenous immunoglobulin injection.

Safety: The patient developed only grade 1 cytokine release syndrome (CRS), but had no immune effector cell-associated neurotoxicity syndrome (ICANS). Only transient hemocytopenia was observed. No new safety risks were found compared to the safety profile in the studies of multiple myeloma indication.

Efficacy: During the 18-month follow-up after infusion of Equecabtagene Autoleucel, the patient's clinical symptoms and imaging characteristics continuously improved. Three months after infusion of Equecabtagene Autoleucel, the patient's strength of extremities improved significantly. He could lift his arms without much effort, and regained his ability to walk. Manual Muscle Testing-8 (MMT-8) score improved from 96 points at baseline to 137 points at the last visit (18 months after infusion). Serum creatine kinase level decreased from 4778 IU/L before infusion to 260 IU/L at the last visit, and myoglobin level decreased from 837 ng/mL before infusion to 66.2 ng/mL at the last visit. Significant improvements were also observed in other quality of life scales. There was no concomitant use of other immunomodulatory therapies during the follow-up.

 PK/PD: The expansion of CAR-T cells in the patient was good after infusion of Equecabtagene Autoleucel. The serum SRP antibody level declined rapidly and remained at a very low level.


The principal investigator of this study, Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology said: This is the first time globally to apply BCMA CAR-T cell therapy to treat IMNM, which is another important breakthrough in the field of autoimmune diseases after the successful treatment of neuromyelitis optica spectrum disorders (NMOSD) with BCMA CAR-T. We look forward to the further development of CAR-T therapy in the field of autoimmunity, bringing hope of cure to patients.”

In addition to the research results published this time, IASO Bio and the investigator team are continuing to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other autoimmune disorders including NMOSD, myasthenia gravis (MG), and chronic inflammatory demyelinating polyneuropathy (CIDP), for the hope of changing the treatment paradigm of autoimmune disorders.