Phase 3 TEMPO-2 trial results published in The Lancet Neurology show once-daily tavapadon significantly improved motor symptoms in early Parkinson’s disease
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Results from the Phase 3 TEMPO-2 trial, published in The Lancet Neurology, showed that tavapadon significantly improved motor symptoms and activities of daily living in people with early Parkinson’s disease compared with placebo. The investigational once-daily oral selective dopamine D1/D5 receptor agonist met the study’s primary endpoint over 26 weeks while demonstrating a manageable safety profile, supporting its potential as a new treatment option for patients early in the course of the disease.
A Selective D1/D5 Agonist for Early Parkinson’s Disease
Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of dopamine-producing neurons, leading to tremor, rigidity, slowed movement, and impaired balance. Although levodopa remains the standard treatment, long-term use is associated with motor complications such as dyskinesia and fluctuating symptom control. Dopamine agonists that primarily target D2 and D3 receptors can also cause adverse effects including excessive daytime sleepiness and impulse control disorders.
Tavapadon is an oral, once-daily, selective partial agonist of dopamine D1 and D5 receptors. By selectively activating these receptors, the therapy aims to improve motor symptoms while potentially reducing the non-motor adverse effects commonly associated with D2/D3 receptor agonists.
Phase 3 TEMPO-2 Trial Met Primary Endpoint
TEMPO-2 (NCT04223193) was a randomized, double-blind, placebo-controlled Phase 3 trial conducted across 75 hospital, academic, and community clinical sites in 13 countries. The study enrolled adults aged 40 to 80 years with early Parkinson’s disease diagnosed within the previous three years who were either treatment-naïve or had received less than three months of prior dopaminergic therapy.
A total of 304 participants were randomly assigned to receive flexible-dose oral tavapadon (5–15 mg once daily; n=151) or placebo (n=153) for 26 weeks.
The primary endpoint evaluated the change from baseline to Week 26 in the combined Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III score, which measures both activities of daily living and motor performance.
Tavapadon achieved a least squares mean reduction of 10.3 points from baseline compared with a 1.2-point reduction in the placebo group. The treatment difference of −9.1 points was statistically significant (95% CI, −11.7 to −6.5; p<0.0001), demonstrating a clinically meaningful improvement in Parkinson’s disease symptoms.
Safety Profile Consistent With Earlier Studies
Most adverse events reported during the trial were mild to moderate and non-serious. Overall, adverse events occurred in 75% of participants receiving tavapadon compared with 54% in the placebo group.
The highest incidence of adverse events occurred during the dose titration period and declined during subsequent dose adjustment and maintenance phases.
The most frequently reported adverse events with tavapadon included:
- Nausea (30% vs 3% with placebo)
- Headache (17% vs 5%)
- Dizziness (16% vs 3%)
Although more participants discontinued treatment in the tavapadon group than in the placebo group, investigators noted a relatively low incidence of somnolence and impulse control disorders, adverse effects that have limited the use of several existing dopamine agonists.
Long-Term Evaluation Continues
The investigators concluded that tavapadon produced significant and clinically meaningful improvements in motor symptoms and daily functioning in people with early Parkinson’s disease. While the 26-week study supports its efficacy and acceptable short-term tolerability, the observation period was insufficient to fully evaluate long-term safety.
An ongoing extension study will continue to assess the durability of clinical benefit, long-term tolerability, and overall safety of tavapadon as a potential new once-daily treatment for early Parkinson’s disease.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.