Short-term efficacy and safety of tavapadon for Parkinson's disease: An exploratory systematic review and meta-analysis of randomized clinical trials

BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and motor and non-motor impairment. Current therapies are limited by motor complications and adverse effects. Tavapadon, a selective dopamine D1/D5 receptor partial agonist, has emerged as a potential therapeutic alternative. Therefore, this study aimed to evaluate the efficacy and safety of tavapadon in patients with PD. METHODS: We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) evaluating tavapadon in patients with PD. The primary outcome was change from baseline in combined MDS-UPDRS Parts II + III. Secondary endpoints included changes in MDS-UPDRS Parts II and III and treatment-related adverse events (TRAEs). Random-effects models were used to estimate pooled mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Four RCTs were included. Tavapadon substantially improved combined MDS-UPDRS II + III scores (MD -8.80; 95% CI -13.51 to -4.09; p = 0.0003). Notable improvements were also observed in Part III (MD -5.44; 95% CI -8.53 to -2.35; p = 0.0006) and Part II (MD -1.66; 95% CI -2.39 to -0.92; p < 0.0001). Tavapadon increased the risk of TRAEs (RR 1.96; 95% CI 1.19 to 3.25; p = 0.0236) with substantial heterogeneity. CONCLUSION: Based on short-term trials, tavapadon demonstrates exploratory evidence for clinically meaningful improvements in motor symptoms and functional outcomes in patients with PD. Despite these benefits, its use is associated with an increased risk of adverse events, highlighting the need for careful patient selection and monitoring until long-term data become available.