Alemtuzumab Treatment Poplation Identified, Siponimod Preserves Retinal Thickness, ATA188 Shows Success in Phase 1

Neurology News Network for the week ending October 15, 2021. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

This week Neurology News Network covered a trio of presentations from ECTRIMS 2021, including the ideal patient population for alemtuzumab treatment, preservation of retinal thickness with siponimod, and updated phase 1 results of ATA188 in progressive MS.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus. This week’s episode was centered around the recently concluded ECTRIMS meeting.

Results from a real-world, 5-year, prospective single-center study showed that most patients with relapsing-remitting multiple sclerosis (RRMS) used alemtuzumab (Lemtrada; Sanofi Genzyme) as a second- or third-line treatment, with it displaying similar efficacy to what was observed in previous extension studies. The data also showed that despite previously failing a disease-modifying therapy (DMT), 76% of patients had progression-free survival and 33% had a cumulative no evidence of disease activity-3 (NEDA-3) status. During the study, all patients reported receiving at least 1 course of alemtuzumab and most (n = 50) received the second. Sixteen patients had a third course and 2 had a fourth. At each of the timepoints, except for month 36, median EDSS was 1.5 (range, 0-7), compared to a median score of 2 (0-7.5) at baseline. More than half (n = 30; 58%) of the patients were relapse-free at the 60-month mark, correlating to an annualized relapse rate (ARR) of 0.12.

Findings presented at ECTRIMS 2021 showed that treatment with siponimod (Mayzent; Novartis) preserved retinal thickness, a marker of neurodegeneration, using optical coherence tomography in patients with secondary progressive multiple sclerosis. Patients in the siponimod group had mean baseline retinal nerve fiber layer thickness lower than those on placebo. After 12 months of treatment, RNFL thickness numerically favored the siponimod group over placebo These results did not hold true at the 24-month mark; however, investigators noted that there were fewer assessments available for RNFL at that time. Compared with placebo, siponimod-treated patients showed reduced retinal thinning at both month 12 and month 24. Notably, siponimod also favored over placebo on subfield changes of retinal thickness and ganglion cell and inner plexiform layers.

Updated results from the small, open-label extension (OLE) portion of the phase 1 study of ATA188 in progressive multiple sclerosis (MS) suggest that the therapy has a sustained clinical benefit over 39 months based on magnetization transfer ratio (MTR), while being safe and tolerable.In total, 7 of the 8 patients enrolled in the OLE achieved sustained disease improvement (SDI) that was steady at all measured time points, with most SDI driven by improvement on Expanded Disability Status Scale (EDSS) scores. For those with sustained EDSS improvement (n = 7), the MTR for unenhancing T2 lesions was improved at 6 months (P = .0796) and significant improvement at 12 months (P = .0213) compared with those without sustained EDSS improvement (n = 15). Overall, trends supported a correlation between increase in MTR signal and improvement in EDSS score as early as 6 months.

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