FDA Clears AbelZeta’s CAR-T Trial for Progressive MS
The multicenter study will begin with 6 to 24 participants to select a dose, followed by about 95 participants divided into two disease-pattern cohorts.
Key Points
- AbelZeta has received FDA clearance to start a Phase 1b/2 trial of C-CAR168 in progressive multiple sclerosis that has not responded to standard therapy.
- The trial will begin with about 6 to 24 patients to select a dose, then expand to about 95 patients across two disease-pattern cohorts.
- C-CAR168 is an autologous (sourced from the patient) bispecific CAR-T that targets CD20 and BCMA and is also being studied in other autoimmune diseases.
AbelZeta has received FDA clearance for an Investigational New Drug application to begin a Phase 1b/2 clinical trial of C-CAR168 in patients with progressive multiple sclerosis refractory to standard therapy. The therapy is an autologous (sourced from the patient) anti-CD20/BCMA chimeric antigen receptor T-cell therapy designed for patients with progressive forms of MS, where treatment options remain limited.
The study is designed to evaluate safety, tolerability, and efficacy. The Phase 1b portion will enroll about 6 to 24 patients with secondary progressive multiple sclerosis or primary progressive multiple sclerosis to identify a recommended Phase 2 dose. The Phase 2 portion will enroll about 95 patients in two independent cohorts:
- Patients with active secondary progressive multiple sclerosis
- Patients with primary progressive multiple sclerosis or non-active progressing secondary progressive multiple sclerosis
Why this trial matters
Progressive multiple sclerosis is marked by gradual worsening of neurological function and disability over time. It includes primary progressive MS, which progresses from disease onset, and secondary progressive MS, which develops after an earlier relapsing-remitting course. Symptoms can include weakness, fatigue, mobility impairment, and cognitive dysfunction.
AbelZeta said the new clearance extends development of C-CAR168 into chronic autoimmune neurological disease. The company also pointed to earlier regulatory progress for the program in systemic lupus erythematosus and lupus nephritis, including FDA clearance of a registrational Phase II trial under RMAT designation and PRIME designation from the EMA’s 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 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. 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 (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.”
About C-CAR168
According to the company, it is intended to drive deep depletion of disease-associated B cells and plasma cells and potentially reset immune function in severe autoimmune disorders.
The company said C-CAR168 is being evaluated across multiple autoimmune indications, including progressive MS, systemic sclerosis, systemic lupus erythematosus, and lupus nephritis. Early clinical data from a Phase 1 first-in-human trial presented at ACR 2025 included secondary progressive multiple sclerosis patients. AbelZeta reported early efficacy signals after treatment, including improvements in gait and neurological function, along with reductions in brain inflammation and lesion size.
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