Title: Efficacy and Safety of Mesdopetam (IRL790) for Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta analysis of Randomized Controlled Trials
Authors: Ashwin Achuthaprasad, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, Ian Walker
Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea
Objective
To evaluate the efficacy and safety of mesdopetam compared with placebo for levodopa‑induced dyskinesia (LID) in Parkinson’s disease (PD).
Background
Mesdopetam (IRL790) is a selective dopamine D3‑receptor antagonist developed to reduce LID without worsening parkinsonism. Multiple randomized trials have investigated its clinical effects across different dose ranges, but results have varied.
Design/Methods
A meta‑analysis of randomized, double‑blind, placebo‑controlled trials was conducted using studies registered on ClinicalTrials.gov to ensure methodological rigor and consistency. Outcomes extracted included the UDysRS total score, ON-time without troublesome dyskinesia (hours), OFF time (hours), MDS-UPDRS‑IV, activities of daily living (MDS-UPDRS‑II), and adverse events (AEs). Mean differences (MD), standardized mean differences (SMD), and risk ratios (RR) for dichotomous outcomes were pooled using inverse‑variance statistical models.
Results
Across 3 studies (n = 323), mesdopetam was non-significant for dyskinesia severity reduction (MD –1.77 points, 95% CI –4.07 to 0.54) [Figure 1]. ON-time without troublesome dyskinesia improvement was nonsignificant (MD –0.47 h, 95% CI –1.25 to 0.31) [Figure 2]. OFF time decreased significantly (MD –0.61 h, 95% CI –1.16 to –0.07) [Figure 3]. UPDRS-IV (MD –0.15 points, 95% CI –0.37 to 0.07) and activities of daily living (SMD –0.17, 95% CI –0.39 to 0.06) were not significant. Overall, any AEs (RR 1.12, 95% CI 0.94–1.34), serious AEs (RR 0.45, 95% CI 0.14–1.42), and falls (RR 1.09, 95% CI 0.45–2.59) were comparable between groups. Fatigue occurred less frequently with mesdopetam, showing a protective effect (RR 0.23, 95% CI 0.06–0.81).
Conclusions
Mesdopetam appears safe and modestly effective for LID, with small improvements in dyskinesia severity and OFF time and no worsening of motor disability. Larger trials are warranted to clarify optimal dosing and confirm clinical benefit.
Citation
Achuthaprasad A, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Efficacy and Safety of Mesdopetam (IRL790) for Levodopa Induced Dyskinesia in Parkinson’s Disease: A Meta analysis of Randomized Controlled Trials. Mov Disord 2026;41(Suppl_1):S1204-S1205.
Figure 1. Forest plot of pooled MD of UDysRS total score.
Figure 2. Forest plot of pooled MD of ON-time without troublesome dyskinesia.
Figure 3. Forest plot of pooled MD of OFF-time.