Title : Efficacy and tolerability of tavapadon for parkinson's disease: A systematic review and meta-analysis
Abstract:
Background: Parkinson’s disease (PD) is a common neurodegenerative disorder in which long-term levodopa therapy is limited by motor fluctuations and dyskinesias. Tavapadon (PF-06649751; CVL-751) is a novel oral selective D1/D5 partial agonist and the first agent of its class to complete a full Phase 1–3 clinical development programme across early and advanced PD. No systematic review or meta-analysis has quantitatively synthesised this evidence base.
Methods: A systematic review and meta-analysis was conducted in accordance with a pre-registered PROSPERO protocol (CRD420261402917). PubMed, CENTRAL, Embase, Scopus, and ClinicalTrials.gov were searched without date restrictions. Randomised placebo-controlled trials of oral tavapadon in adults with idiopathic PD were included. Primary outcomes were change from baseline in MDS-UPDRS Part III, Part II, and Parts II+III combined scores. Meta-analyses were performed in RevMan 5.4 using a random-effects inverse-variance model.
Results: Five randomised placebo-controlled trials were included across early and advanced PD populations (Riesenberg et al. 2020; NCT02687542; TEMPO-1, TEMPO-2, TEMPO-3).. Tavapadon demonstrated statistically significant improvement in MDS-UPDRS Part III at weeks 14–15 (MD −6.15, 95% CI −7.94 to −4.36; I²=4%; P<0.00001) and week 26 (MD −6.50, 95% CI −10.65 to −2.35; I²=93%; P=0.002). At week 26, significant improvements were additionally observed in MDS-UPDRS Part II (MD −1.79, 95% CI −2.63 to −0.95; I²=61%; P<0.0001) and MDS-UPDRS Parts II+III combined (MD −8.33, 95% CI −13.15 to −3.50; I²=91%; P=0.0007).
Conclusions: This first systematic review and meta-analysis of the complete tavapadon clinical development programme demonstrates significant and clinically meaningful improvements in motor function across PD disease stages, supporting selective D1/D5 agonism as a viable pharmacological approach for PD.
