An investigational allogeneic CAR T-cell therapy depleted B cells in the blood and cerebrospinal fluid of people with progressive multiple sclerosis (MS), while most evaluable participants had stable or improved disability scores three months after treatment.
Azercabtagene zapreleucel, or azer-cel, is the first allogeneic CD19-directed CAR T-cell therapy to be evaluated clinically in progressive MS, according to developer TG Therapeutics. The company presented initial results from the ongoing TG-Azercel-101 Phase I study at the joint ACTRIMS-ECTRIMS meeting in Toronto.
Unlike autologous CAR T-cell therapies manufactured from an individual patient’s cells, azer-cel is produced from healthy donor T cells and stored for off-the-shelf use. The cells are engineered to target CD19, a protein expressed on B cells, with the aim of producing deeper B-cell depletion in the blood, tissues, and cerebrospinal fluid.
The study included 26 people with primary progressive, active secondary progressive, or non-active secondary progressive MS. All had experienced disability progression independent of relapse activity during the previous year despite high-efficacy treatments, and all had previously received anti-CD20 therapy.
Participants received bendamustine lymphodepletion followed by a single infusion containing between 30 million and 500 million CAR T cells. At the September 3 data cutoff, median follow-up was 4.9 months.
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 participants experienced cytokine release syndrome and two developed neurotoxicity, all at grade 1 or 2. Eleven participants experienced grade 3 or higher treatment-emergent adverse events, while four had serious adverse events.
Peripheral B-cell counts fell below 10 cells per microliter in 25 of 26 participants. Among 21 people with paired cerebrospinal fluid samples, the median number of CD19-positive B-cell events declined by 52.3 percent at day 10.
At day 90, Expanded Disability Status Scale scores were stable or improved in 16 of 18 evaluable participants. Three recorded improvements of at least two points, including one with a four-point reduction. Seven of eight participants assessed at six months remained stable or improved.
“These initial azer-cel results are particularly encouraging given that all patients entered the study with progressive disability despite prior treatment with high-efficacy therapies,” said TG Therapeutics CEO Michael Weiss in a press release.
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