IND for NMOSD CAR T-Cell Therapy Approved by Chinese Health Authorities

An investigational BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy from IASO Biotherapeutics, CT103A (equecabtagene autoleucel), received investigational new drug (IND) application approval from China's National Medical Products Administration (NMPA) for an expanded indication in neuromyelitis optica spectrum disorder (NMOSD).¹

Notably, the cell therapy, which is being co-developed with Innovent Biologics, also recently had its marketing application accepted by the NMPA for the treatment of relapsed/refractory multiple myeloma (r/r MM).

In data from an investigator-initiated clinical study (NCT04561557) that included 12 patients with NMOSD, all patients who received CT103A showed improved Expanded Disability Status Scale (EDSS) scores, 50% showed improvement in visual acuity, 67% showed improvement in walking ability, and 75% demonstrated improved bladder function. No disease recurrence was observed in 11 of 12 patients after a median follow-up of 5.5 months.

"As one of the first companies to conduct research on CAR-T to treat autoimmune diseases worldwide, our BCMA CAR T-cell therapy represents a significant milestone for investigator initiated trial data of relapsed and refractory NMOSD, an autoimmune disease with serious complications, blindness, and paralysis,” Wen (Maxwell) Wang, MD, PhD, chief executive officer and chief medical officer, IASO Biotherapeutics, said in a statement regarding the news.¹

In terms of safety, there were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in the 12 patients as of March 20, 2022. However, grade 1-2 cases of cytokine release syndrome (CRS) were observed in all 12 patients.

The ongoing phase 1, open-label clinical trial is open to patients diagnosed with relapsed/refractory NMOSD, myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and immune-mediated necrotizing myopathy (IMNM) whose disease was poorly-controlled and had prior treatment for at least 1 year with an immunosuppressant; prior treatment with at least 1 first-line therapy for more than 3 months for patients with CIDP; or prior treatment with corticosteroid therapy for at least 1 month and immunosuppressants for more than 3 months for patients with IMNM. Patients with a history of autoimmune hemolytic disease or solid organ transplantation, patients prone to allergies or with a history of serious allergies are excluded from the study, as are patients who have been treated with alemtuzumab within 6 months prior to apheresis, or treated with fludarabine or cladribine within 3 months prior to apheresis.

Of the 12 patients who had been treated as of the March 20, 2022 cutoff date, 3 patients received an intravenous infusion of 0.5×10⁶ CAR-T cells/kg and 9 received 1.0×10⁶ CAR-T cells/kg. Patients underwent leukapheresis for the isolation of peripheral blood mononuclear cells which were used to produce the CT103A cells. Cyclophosphamide and fludarabine were administered during leukapheresis. The primary end points for the study are types and incidences of dose-limiting toxicities and incidences and severity of adverse events. Secondary end points include the decrease in the concentration of AQP4-IgG titers in the serum after treatment for patients with NMOSD, and decreases in the concentration of related abnormal antibody titers in the serum after treatment for patients with MG, CIPD, and IMNM. The absolute and relative levels of B-cells and their subsets will also be evaluated. For patients with NMOSD, the proliferation of CT103A cells and the copy number of the BCMA CAR gene in peripheral blood after treatment will additionally be evaluated.

“The use of CAR-T cell products has been widely accepted in the treatment of hematologic malignancy, but has been rarely reported in the treatment of autoimmune diseases... ” Wang said in a previous statement in May 2022.² “[T]he new therapeutic strategy offered by IASO Bio with equecabtagene autoleucel can provide an opportunity to reverse and ameliorate organ damage and improve the quality of life in NMOSD patients. It may provide a new treatment option for patients with poorly controlled NMOSD by existing drugs. We expect that this product candidate will be available soon to NMOSD patients in China and around the world.”

The study’s estimated completion date is December 31, 2023. CT103A previously received breakthrough therapy designation from the NMPA for the treatment of r/r MM in February 2021, and orphan drug designation from the US FDA for the treatment of r/r MM in February 2022.

REFERENCES

1. World's first CAR-T for NMOSD treatment, IASO Biotherapeutics' equecabtageneautoleucel, receives IND approval by NMPA. News release. IASO Biotherapeutics. August 19, 2022. http://www.iasobio.com/info.php?id=198 

2. IASO Biotherapeutics’ equecabtageneautoleucel, the world’s first CAR-T for treatment of NMOSD, receives IND application acceptance by NMPA. News release. IASO Biotherapeutics. May 20, 2022. http://www.iasobio.com/info.php?id=188