IASO Reports Positive First Uses of Eque-Cel for CNS Autoimmunity


The company has reported data in NMOSD, myasthenia gravis, and necrotizing myopathy over the last several months.

IASO Bio has steadily been exploring the use of its investigational autologous BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy equecabtagene autoleucel (eque-cel) in autoimmune indications, with promising reports of use in patients with neuromyelitis optica spectrum disorder (NMOSD), myasthenia gravis (MG), and immune-mediated necrotizing myopathy (IMNM).1,2,3

The recent case reports are part of a clinical phase 1 program (NCT04561557) investigating eque-cel in nervous system autoimmunity indications, under principal investigator Professor Wei Wang from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

The company recently published data on 2 participants with MG, a 33-year old female and a 60-year old female, who received 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg, respectively. After receiving eque-cel, 1 developed grade 1 Cytokine release syndrome (CRS). There were no cases of Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). Serious cases of hemocytopenia recovered within 4 weeks of infusion. Starting at 3 months after infusion, the patients showed significant improvement in limb strength and vital capacity, and sustained improvement in 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 Score (mRS). The patients received only low dose pyridostigmine during the follow-up period as immunomodulatory therapy.1

“MG has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of MG to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality. In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients,” Wang said in a statement.1 IASO received investigational new drug application (IND) clearance from the FDA in April to investigate eque-cel in patients with MG.4

READ MORE: Cartesian Therapeutics’ mRNA CAR-T Descartes-08 Continues to Show Efficacy in Phase 2b Myasthenia Gravis Trial

IASO presented data from 12 patients with aquaporin-4 (AQP4) antibody-positive relapsed/refractory NMOSD at the 2024 European Academy of Neurology (EAN) Annual Meeting, held June 29-July 2, in Helsinki, Iceland. All participants had been treated with at least 1 immunosuppressant for over a year but had poor symptom control. In these patients, the company stated that eque-cel demonstrated good tolerability and safety, durable pathogenic antibody clearance, and potential clinical efficacy.2

“This study was the world's first clinical trial of CAR-T therapy in the field of AQP4-mediated relapsed/refractory NMOSD. It not only demonstrated the encouraging efficacy and controllable safety of Eque-cel in NMOSD but also elucidated the cellular dynamics and immunological characteristics of CAR-T therapy for central nervous system autoimmune diseases. This provides a new therapeutic approach for antibody-mediated autoimmune diseases and also provides scientific insights into refining CAR-T cell therapies for autoimmune diseases,” Wang said in a statement about the NMOSD data.2

Lastly, IASO also published data on eque-cel’s use in a 25-year-old male patient with a 7-year history of SRP antibody-positive refractory IMNM. The patient had received 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, experienced repeated relapses, and was paralyzed and bedridden prior to enrollment.3

After receiving eque-cel, the patient developed grade 1 CRS but had no ICANs. Other immunomodulatory therapies were not used during follow-up. Three months after infusion, the patient was able to lift his arms without much effort and regained his ability to walk. The patient improved from 96 points at baseline to 137 points at 18 months post-infusion on Manual Muscle Testing-8 (MMT-8), decreased from 4778 IU/L before infusion to 260 IU/L in serum creatine kinase, and decreased from 837 ng/mL before infusion to 66.2 ng/mL in myoglobin levels at the last visit. Investigators also observed significant quality of life improvements.3

“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 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,” Wang said about the case study.3

1. IASO Bio’s Equecabtagene Autoleucel for Refractory Myasthenia Gravis (MG) Case Report Published in EMBO Molecular Medicine. News release. IASO Bio. February 29, 2024. https://www.iasobio.com/phone/info.php?id=229
2. IASO Bio Presented Clinical Data and Single-cell Analysis of Equecabtagene Autoleucel for the Treatment of Central Nervous System Autoimmunity in Oral Presentation at EAN 2024. News release. IASO Bio. July 1, 2024. https://www.iasobio.com/phone/info.php?id=244
3. 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). News release. IASO Bio. February 1, 2024. https://www.iasobio.com/phone/info.php?id=228
4. IASO Bio announces U.S. FDA approval of investigational new drug application for BCMA CAR-T equecabtagene autoleucel for generalized myasthenia gravis. News release. IASO Biotechnology. April 5, 2024. Accessed April 7, 2024. https://www.iasobio.com/info.php?id=234
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