Preliminary data shows positive results of ATA188 for progressive MS

Preliminary data of a phase 1, open-label extension (OLE) trial investigating ATA188 for progressive MS showed that the drug was generally well tolerated and drove sustained disability improvement (SDI) in a significant proportion of patients. Moreover, improved magnetisation transfer ratios (MTRs) were observed in patients with SDI, suggesting possible remyelination [1].

Evidence suggests that Epstein-Barr virus is strongly involved with the pathogenesis of MS [2,3]. To this end, the current trial assessed ATA188 as a potential therapy for patients with progressive MS. ATA188 is an investigational, off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy. In total, 25 patients with progressive MS followed a 12-month dose-escalation protocol of ATA188. Hereafter, patients were invited to enter a 4-year OLE period. Prof. Douglas Arnold (McGill University, Canada) presented preliminary data of the study.

SDI, based on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk, was demonstrated in 7 out of 24 patients at 12 months. Six out of 7 patients who achieved SDI and 12 out of 17 patients who did not achieve SDI entered the OLE. During the OLE, 2 non-SDI patients improved to SDI. MTRs, an MRI marker of myelin density, improved significantly in patients who achieved sustained EDSS improvement at any time compared with patients who did not. MTRs improved in T2 lesions at 12 months, with a median change for patients with sustained EDSS of 0.134 versus -0.030 in patients without sustained EDSS (P=0.021), and at 6 months (P=0.080). Moreover, numerical MTR improvements in normal-appearing brain tissue were observed at 12 months (median change for sustained EDSS, 0.082 vs no sustained EDSS, 0.005; P=0.162). In general, the authors detected a trend supporting an association between improvement in MTR signal and a reduction in EDSS score. Prof. Arnold argued that the MTR data showed that structural changes, suggestive of remyelination, may be the mechanism behind sustained EDSS improvement.

In total, 25 patients received at least one dose of ATA188 and were assessed for safety. A favourable safety profile was observed. No grade >3 adverse events, dose-limiting toxicities, cytokine-release syndrome, or graft-versus-host disease were reported. One grade 3 MS relapse –that was possibly related to treatment– occurred. A randomised, placebo-controlled trial is needed to confirm the encouraging results of this trial.

1. Bar-Or A, et al. Updated open-label extension clinical data and new magnetization transfer ratio imaging data from a Phase 1 study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus targeted T-cell immunotherapy for progressive multiple sclerosis. P638, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Abrahamyan S, et al. J Neurol Neurosurg Psychiatry. 2020;91(7):681–686.
3. Bar-Or A, et al. Trends Mol Med 2020;26(3):296–310.

 

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Posted on 9 December 202114 December 2021