IASO Bio Announces U.S. FDA Approval of Investigational New Drug Application for BCMA CAR-T Equecabtagene Autoleucel for Generalized Myasthenia Gravis

SHANGHAI and NANJING, CHINA, and SAN JOSE, Calif., April 4, 2024 /PRNewswire/ -- IASO Biotechnology ("IASO Bio"), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing innovative cell therapy and antibody products, is pleased to announce that the Investigational New Drug (IND) application for its BCMA CAR-T (Equecabtagene Autoleucel, Eque-cel) has been approved by the U.S. Food and Drug Administration (FDA) for use in U.S. clinical trials for generalized myasthenia gravis (gMG). The Chinese IND for this indication of Eque -cel was approved by the NMPA in January this year.

Two subjects with refractory MG were enrolled in an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557). One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK-IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the dose of 1.0×10⁶ CAR-T/Kg. Results of the study were published in EMBO Molecular Medicine in February this year.

Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. 

Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, 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). 

PK/PD: Eque-cel expanded well after infusion. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. 

Professor Wei Wang of Tongji Hospital, Tongji Medical School of Huazhong University of Science and Technology, the principal investigator of this clinical study, said, "The existing treatment options for autoimmune diseases are limited.  Autoimmune diseases are difficult to cure, and recurrent attacks bring great physical and psychological burden to patients and their families. In collaboration with IASO Bio, we have taken the lead in applying BCMA CAR-T, an advanced cell therapy, to a variety of serious autoimmune diseases, including MG, and have achieved very good clinical efficacy.  We have published several research papers in leading scientific journals. The US IND approval of Eque-cel for the treatment of gMG, a several autoimmune disease, represents a recognition of the FDA of the potential clinical value of our research direction.  We will further explore the application of BCMA CAR-T in treating additional severe autoimmune diseases."

Ms. Jinhua Zhang, Founder and Chairman of IASO Bio, stated, "We are very pleased that Eque-cel has been approved for clinical trial   for gMG in the United States. This is IASO's first IND approval in the US to apply CAR-T therapies in autoimmune diseases. This not only represents the international recognition of our R&D strength and the potential value of our cell therapy product in the field of autoimmunity, but also an important milestone for IASO to start a new journey in the global autoimmune market. I would like to thank the clinicians who helped us conduct the clinical trial, and the patients and their families who participated in the clinical trial for their trust in us. Seeing patients with severe autoimmune diseases who have been repeatedly tormented by the disease and cannot take care of themselves return to normal life after treatment with Eque-cel is the biggest motivation for our R&D effort. We will actively promote the clinical development of Eque-cel in the US to provide a more effective and longer-lasting treatment option for MG patients around the world. At the same time, we are committed to expanding breakthrough cell therapies to a broader range of autoimmune diseases, and strive to improve the global treatment landscape of such diseases so that more patients suffering from debilitating autoimmune diseases can return to a normal, healthy life."

About MG

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder. The main clinical manifestation of MG is a decrease in muscle strength in local or systemic muscles, which can affect eye, respiratory and limb muscles and other important muscle groups, which has a huge negative impact on the patient's quality of life, and dysphagia or breathing difficulty caused by a myasthenic crisis can be life-threatening. The main pathogenic antibodies in MG include AChR, MuSK and LRP4 antibodies. A very small number of patients have no detectable antibodies in their serum^[1]. MG can occur at any age and is slightly more common in women than in men^[2]. According to relevant studies, the incidence rate of MG in the United States is 3.1/100,000 people and the prevalence rate is 37.0/100,000 people^[3]. It is estimated that the number of people with MG incidence in the United States in 2023 was 10,358, and the number of patients with MG was 123,628.

About IASO Bio

IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production.

The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of R/RMM.

Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit http://www.iasobio.com or www.linkedin.com/company/iasobiotherapeutics.

Reference              

1.  中国重症肌无力诊断和治疗指南 (2020) 版

2.  Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study - The Lancet Regional Health – Western Pacific.

3.  Rodrigues, E. et al. Incidence and prevalence of myasthenia gravis in the United States: A claims-based analysis. Muscle Nerve 69, 166–171 (2024).

SOURCE IASO Bio