Title: Mavoglurant Shows Modest Efficacy in Reducing OFF-time but no Consistent Motor Benefit in Parkinson’s Disease: A Meta-analysis of Randomized Controlled Trials (P6-17.016)
Authors: Zain Abidin, Jamir Pitton Rissardo, Omar Elmandouh, Ana Leticia Fornari Caprara, and Ian M. Walker
Conference: 2026 AAN, Chicago, IL
Objective
To assess the efficacy of mavoglurant, a metabotropic glutamate receptor 5 (mGluR5) antagonist, on motor fluctuations and dyskinesia in Parkinson’s disease (PD).
Background
Glutamatergic overactivity contributes to levodopa-induced dyskinesia (LID) in PD. Mavoglurant, an mGluR5 antagonist, was developed to mitigate LID and improve motor control, but trial results have been inconsistent.
Design/Methods
We systematically searched randomized controlled trials comparing mavoglurant with placebo in patients with Parkinson's disease who had motor fluctuations or dyskinesia. Continuous outcome data were extracted, including daily OFF-time, ON-time without troublesome dyskinesia, dyskinesia severity (Lang-Fahn scale and mAIMS), and UPDRS motor and complications scores. Effect sizes were pooled using standardized mean differences (SMD) or mean differences (MD), depending on whether outcomes were measured on the same scale. A random-effects model with DerSimonian–Laird estimation was applied to account for between-study variability. Heterogeneity was assessed using I² and τ² statistics, prediction intervals were calculated, and subgroup analyses were performed to evaluate potential dose-response effects across doses ranging from 20 to 300 mg.
Results
Four trials (PMID 21484867, 23853029, 24007304, and 27214258) were included. Mavoglurant significantly reduced OFF-time compared to placebo (SMD = –0.67, 95% CI: –0.84 to –0.86, p < 0.001). However, ON-time without troublesome dyskinesia showed no significant improvement (SMD = 0.02, 95% CI: –0.21 to 0.25). Dyskinesia severity improved on mAIMS (MD = –2.17, 95% CI: –3.50 to –0.85, p = 0.0013), and fixed-effect (MD -0.34, 95% CI -0.53 to -0.15, p = 0.01) Lang-Fahn, but were not significant under random-effects or for UPDRS-IV. Subgroup analysis suggested greater OFF-time reduction at higher doses (≥200 mg). Publication bias was minimal.
Conclusions
Mavoglurant modestly reduces OFF-time and improves dyskinesia severity on mAIMS but does not consistently enhance ON-time or UPDRS scores. These findings highlight the limited clinical utility of mGluR5 antagonism in PD and underscore the need for alternative strategies to manage LID.
Citation
Abidin Z, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. Mavoglurant Shows Modest Efficacy in Reducing OFF-time but no Consistent Motor Benefit in Parkinson’s Disease: A Meta-analysis of Randomized Controlled Trials (P6-17.016). Neurology 2026;106(11_suppl):1163. doi: 10.1212/WNL.0000000000215017.
Figure 1. Forest plot shows mavoglurant reduces OFF-time versus placebo, with greater effect at higher doses; moderate heterogeneity observed.
Figure 2. Forest plot shows no significant improvement in ON-time without troublesome dyskinesia with mavoglurant; substantial heterogeneity across doses.
Figure 3. Forest plot shows modest improvement in dyskinesia severity with mavoglurant, with variable dose-response effects and moderate heterogeneity.