Objective:

To report initial safety, B-cell depletion, and disability outcomes with azer-cel in people with progressive multiple sclerosis.

Approach:

• Study: The ongoing Phase I TG-Azercel-101 study enrolled 26 people with primary progressive or secondary progressive MS and recent disability progression despite high-efficacy treatment; all had previously received anti-CD20 therapy.
• Treatment and follow-up: Participants received bendamustine lymphodepletion followed by one infusion of 30 million to 500 million donor-derived, CD19-directed CAR T cells. Median follow-up at the September 3 cutoff was 4.9 months.

Key Findings:

• Peripheral B-cell counts fell below 10 cells/µL in 25 of 26 participants.
• Among 21 participants with paired cerebrospinal fluid samples, median CD19-positive B-cell events declined 52.3% by day 10.
• At day 90, disability scores were stable or improved in 16 of 18 evaluable participants; three improved by at least two points. Seven of eight assessed at six months remained stable or improved.
• No dose-limiting toxicities, grade 3 or higher cytokine release syndrome, grade 2 or higher immune effector cell-associated neurotoxicity syndrome, graft-versus-host disease, or immune effector cell-associated hemophagocytic syndrome were reported. Two partici…

Interpretation:

These are initial findings from an ongoing Phase I study. TG Therapeutics CEO Michael Weiss described the results as encouraging given participants’ progressive disability despite prior high-efficacy treatment.

Limitations:

• The study is ongoing, with a median follow-up of 4.9 months at the reported cutoff.
• Disability outcomes were available for 18 participants at day 90 and eight at six months.
• The context provides no comparator group or detailed results beyond the initial report.

Sources:

• Article context; initial results from TG-Azercel-101 presented at the joint ACTRIMS-ECTRIMS meeting