FDA Clears AbelZeta IND for Phase 1b/2 Trial of Bispecific CAR-T C-CAR168 in Progressive Multiple Sclerosis
核心洞察
The FDA has cleared AbelZeta's IND application to launch a Phase 1b/2 trial of C-CAR168, an anti-CD20 (搜索)/BCMA (搜索) bispecific CAR-T, in progressive multiple sclerosis (搜索) refractory to standard therapy.
The clearance extends C-CAR168 development into refractory chronic autoimmune neurological disease, following RMAT-designated Phase II clearance in lupus nephritis (搜索) and EMA PRIME designation.
Phase 1b will enroll roughly 6 to 24 SPMS or PPMS patients to identify the recommended Phase 2 dose, with Phase 2 enrolling about 95 patients in two cohorts.
AbelZeta Pharma, Inc. (搜索) announced on Sept. 14, 2026 that the U.S. Food and Drug Administration (搜索) has cleared its Investigational New Drug application to initiate a Phase 1b/2 clinical trial of C-CAR168, an autologous anti-CD20 (搜索)/BCMA (搜索) bispecific chimeric antigen receptor T-cell therapy, in patients with progressive multiple sclerosis (搜索) refractory to standard therapy. The company, which maintains centers of excellence in Rockville, Maryland and Shanghai, said the clearance expands its C-CAR168 development program into refractory chronic autoimmune neurological disease.
The decision follows two recent regulatory milestones for C-CAR168 in refractory systemic lupus erythematosus (搜索) (SLE), including lupus nephritis (搜索) (LN): FDA clearance, under the Regenerative Medicine Advanced Therapy (RMAT) designation, of a multicenter registrational Phase II clinical trial, and PRIority MEdicines (PRIME) designation from the European Medicines Agency (搜索)'s Committee for Medicinal Products for Human Use (CHMP).
"The FDA clearance of this Phase 1b/2 study represents another important step in realizing the potential of C-CAR168 across refractory chronic autoimmune diseases," said Tony (Bizuo) Liu, Chairman and Chief Executive Officer of AbelZeta. "Progressive multiple sclerosis (搜索) can cause significant and irreversible neurological disability, and there remains a considerable unmet medical need for therapies capable of addressing the underlying immune dysfunction driving disease progression."
Trial Design and Patient Cohorts
The multi-center Phase 1b/2 study is designed to evaluate the safety, tolerability, and efficacy of C-CAR168 in patients with progressive multiple sclerosis (搜索) who have an inadequate response to standard therapies. Phase 1b will enroll approximately 6 to 24 patients with secondary progressive MS (SPMS) or primary progressive MS (PPMS) to identify the recommended Phase 2 dose. The Phase 2 portion will enroll approximately 95 patients across two independent cohorts — one with active SPMS and the other with PPMS or non-active progressing SPMS — to further assess safety and clinical efficacy.
Early Efficacy Signals
Liu pointed to updated preliminary efficacy data supporting the program's advance. "Based on updated preliminary efficacy data, including early and sustained Expanded Disability Status Scale (EDSS) reduction and functional improvement observed in two secondary progressive multiple sclerosis (搜索) (SPMS) patients, one with active and the other with non-active disease, one of whom had over one year of follow-up, we remain cautiously optimistic that the deep immune-cell depletion and reset enabled by C-CAR168 can provide meaningful and durable benefit to these patients."
Early clinical data from a Phase 1 first-in-human trial, presented at ACR 2025, included SPMS patients. Following treatment with C-CAR168, those patients showed promising early efficacy signals, including improvements in gait and neurological function and reductions in brain inflammation and lesion size.
Mechanism and Broader Development
C-CAR168 is designed to achieve deep depletion of disease-driving B cells and plasma cells, with the goal of inducing an immune reset in patients with severe autoimmune diseases. Beyond progressive MS, the therapy is being evaluated across multiple autoimmune indications, including systemic sclerosis (搜索) (SSc), SLE, and LN.
Disease Burden and Unmet Need
Multiple sclerosis is a chronic immune-mediated disease that damages the brain and spinal cord, producing symptoms such as weakness, fatigue, mobility impairment, and cognitive dysfunction. It affects approximately 2.8 million people worldwide, with a prevalence of 35.9 per 100,000 population and an incidence of 2.1 new cases per 100,000 people annually.
Progressive multiple sclerosis (搜索) is characterized by gradual worsening of neurological function and disability over time. It includes PPMS, which progresses from disease onset, and SPMS, which develops after an initial relapsing-remitting course. According to the company, treatment options for these patients remain limited.
AbelZeta describes itself as a global clinical-stage biopharmaceutical company focused on developing cell-based therapeutic products, with a pipeline comprising multiple CAR-T therapies advanced through research and development at its own GMP facilities.