Tavapadon Improves Motor Symptoms in Parkinson’s Disease: Lancet
USA: A 27-week study published in The Lancet Neurology has revealed that tavapadon, a selective dopamine D1/D5 receptor agonist, produced significant and clinically meaningful improvements in motor symptoms among patients with Parkinson’s disease. The treatment was generally well tolerated, with somnolence reported in 4% of tavapadon-treated patients versus 3% with placebo, while hallucinations occurred in 4% of patients receiving tavapadon.
The findings are from the phase 3 TEMPO-2 trial, published in The Lancet Neurology by Prof. Hubert H. Fernandez, Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA, and colleagues. The study evaluated the safety, tolerability, and efficacy of flexible-dose tavapadon in adults with early-stage Parkinson's disease.
Parkinson's disease is commonly treated with dopaminergic therapies, but existing options have important drawbacks. Long-term levodopa therapy can lead to motor complications, while dopamine agonists targeting D2/D3 receptors are associated with troublesome non-motor adverse effects. Tavapadon is a once-daily oral selective dopamine D1/D5 receptor agonist developed to improve motor function while potentially reducing these limitations.
Researchers evaluated tavapadon in the phase 3, randomized, double-blind, placebo-controlled TEMPO-2 trial involving adults aged 40–80 years with early-stage Parkinson's disease across 75 centers in 13 countries. Participants received flexible-dose tavapadon (5–15 mg once daily) or placebo for 27 weeks. The primary endpoint was the change in the combined MDS-UPDRS Parts II and III score, assessing activities of daily living and motor function.
Key findings from the study include:
- The trial enrolled 304 participants, with a mean age of 62.9 years and an average disease duration of 0.86 years; 56% were men.
- Tavapadon produced a significantly greater improvement in MDS-UPDRS Parts II and III scores than placebo, with a least squares mean reduction of 10.3 points versus 1.2 points, representing a treatment difference of 9.1 points (p<0.0001).
- Overall, 26% of participants discontinued the study, with discontinuations occurring more frequently in the tavapadon group (38%) than in the placebo group (15%), primarily due to adverse events.
- Most adverse events were mild to moderate and non-serious, although they occurred more often with tavapadon (76%) than placebo (55%).
- The most common adverse events associated with tavapadon were nausea (30%), headache (17%), and dizziness (16%), with most occurring during the dose-titration phase.
The investigators noted that although tavapadon demonstrated meaningful clinical benefits with a low incidence of somnolence and impulse control disorders, the 27-week follow-up limits conclusions regarding long-term safety and tolerability. They emphasized that an ongoing extension study is expected to provide additional evidence on the drug's long-term efficacy and safety profile.
Reference:
Fernandez, H. H., Bhatia, P., Cloud, L., Fietzek, U. M., Matarazzo, M., Molho, E., Peckham, E., Tarakad, A., Combs, C., Leoni, M., Chang, I., Tringali, S., Boiser, J., Sanchez, R., & Zadikoff, C. (2026). Safety, tolerability, and efficacy of flexible-dose tavapadon for Parkinson's disease (TEMPO-2): A phase 3, randomised, placebo-controlled, double-blind trial. The Lancet Neurology, 25(8), 721-730. https://doi.org/10.1016/S1474-4422(26)00215-2
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