China-based IASO Biotherapeutics has announced the interim results of a Phase I investigator-initiated-trial (ITT) for its BCMA chimeric antigen receptor autologous T (CAR-T) cell therapy equecabtagene autoleucel (CT103A) in neuromyelitis optica spectrum disorder (NMOSD). The study (NCT04561557) is the world’s first to assess a CAR-T therapy in aquaporin 4 (AQP4)-mediated recurrent/refractory NMOSD, focusing on the safety and efficacy of the drug in this autoimmune disorder.
Study Details
The study enrolled patients with refractory NMOSD with positive AQP4 antibodies, preliminarily proving the tolerability and safety of the BCMA CAR-T therapy. The results showed signs of lasting elimination of pathogenic antibodies and potential clinical efficacy. After a median follow-up of 5.5 months in 12 subjects, no NMOSD recurrence was observed in 11 (92%) subjects. Equecabtagene autoleucel generally reduced the scores of the extended Disability Status Rating Scale (EDSS) for NMOSD subjects, with improvements in vision, walking ability, and rectal and bladder functions. The serum AQP4 antibody level decreased significantly and remained low. All 12 subjects experienced grade 1 to 2 cytokine release syndrome (CRS), but no immune effector cell-associated neurotoxicity syndrome (ICANS).
NMOSD Context
NMOSD, an autoimmune disease of the central nervous system with high recurrence and disability rates, was included on China’s rare disease list in May 2018. Most NMOSD sufferers have serious sequelae. Equecabtagene autoleucel is under co-development with Innovent Biologics (HKG: 1801) and obtained breakthrough therapy designation (BTD) for use in recurrent refractory multiple myeloma (r/r MM) in February 2021. In January 2022, US-based Sana Biotechnology Inc. (NASDAQ: SANA) entered into an agreement with both Chinese companies, obtaining non-exclusive commercialization rights for certain in vivo gene therapy and ex vivo hypoimmune cell therapy applications. The drug is also being assessed for safety and efficacy in other antibody-mediated autoimmune diseases, including myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and immune-mediated necrotizing myopathy.
Future Implications
The positive interim results from the Phase I trial of equecabtagene autoleucel in NMOSD highlight the potential of this innovative CAR-T therapy to address significant unmet medical needs. IASO Biotherapeutics’ collaboration with Innovent Biologics and Sana Biotechnology underscores the global interest in advancing treatments for rare and complex autoimmune diseases.-Fineline Info & Tech
