Objective: Report baseline characteristics for patients with multiple system atrophy (MSA) entering a study to assess the safety and efficacy of alpha-synuclein (α-syn) monoclonal antibody treatment with Lu AF82422.
Background: The pathological hallmark of MSA is the presence of glial cytoplasmic inclusions in oligodendroglial cells, consisting mostly of aggregated α-syn. Lu AF82422 targets all major forms of extracellular α‑syn and inhibits seeding and spreading of pathological form(s) of α‑syn in preclinical models and has shown target engagement in a Phase 1 clinical trial. The ongoing AMULET study is a Phase 2 double-blind, placebo-controlled trial (NCT05104476) of Lu AF82422 (IV infusion every 4 weeks) in patients with MSA in the US and Japan.
Method: Patients (40-75y) with a diagnosis of possible or probable MSA (parkinsonian or cerebellar subtypes), with <5 years from onset of motor symptoms were eligible for inclusion. Patients had to have a Unified MSA Rating Scale (UMSARS) Part I score ≤16 (omitting item 11) at screening, a Montreal Cognitive Assessment (MoCA) score of ≥22 and anticipated survival of ≥3 years. The primary endpoint is disease progression, as assessed by the change from baseline in the Total-UMSARS (Part I+II) score at end of double-blind treatment (48-72 weeks).
Results: 61 patients (male=52.5%, female=47.5%) with MSA (32.8%/67.2% MSA-P/MSA-C; 36.1%/63.9% possible/probable MSA) were randomized and treated. Overall, the mean±SD age was 60.8±7.7y, time since onset of symptoms was 3.3±1.2y & time since MSA diagnosis was 1.4±1.1y. Of these, 46 (75.4%) had MRI abnormalities supporting the diagnosis of MSA. Mean±SD UMSARS Part I was 16.6±3.8, Total-UMSARS was 35.5±8.6 & EQ-5D VAS was 64.4±18.4. According to clinical global impression, 21 (34.4%) patients were mildly impaired, 35 (57.4%) moderately & 3 (4.9%) were severely impaired. Overall, 34 (55.7%) patients were receiving concomitant treatment for MSA symptoms (n=20 [32.8%)] for parkinsonian & n=24 [39.3%] for autonomic symptoms).
Conclusion: Study randomization is complete and baseline characteristics are consistent with a population of patients with MSA who are still relatively early in their disease course,1 and who might be good candidates to assess the slowing of clinical progression with a therapy preventing α-syn accumulation.
References: 1. Singer & Low. Clin Auton Res. 2015;25(1):47-52.
To cite this abstract in AMA style:
W. Singer, A. Takeda, L. Kjærsgaard, J. Wiedemann, A. Berger, A. Varrone, A. Bidani, D. Meulien. Baseline characteristics for patients with multiple system atrophy entering a randomized, controlled study of the anti-α-synuclein monoclonal antibody Lu AF82422 [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/baseline-characteristics-for-patients-with-multiple-system-atrophy-entering-a-randomized-controlled-study-of-the-anti-%ce%b1-synuclein-monoclonal-antibody-lu-af82422/. Accessed November 21, 2024.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-characteristics-for-patients-with-multiple-system-atrophy-entering-a-randomized-controlled-study-of-the-anti-%ce%b1-synuclein-monoclonal-antibody-lu-af82422/