For People with Parkinson Disease, Tavapadon Adjunctive Therapy to Levodopa Increased Good ON Time

Results from the TEMPO-3 clinical trial (NCT04542499) presented at the American Academy of Neurology (AAN) 2025 Annual Meeting showed that tavapadon (AbbVie, North Chicago, IL) was effective as an adjunctive therapy to levodopa for the treatment of Parkinson disease (PD) in adults with motor fluctuations. Adjunctive tavapadon therapy was associated with an increase in daily good ON time without troublesome dyskinesia and a reduction in daily OFF time.

TEMPO-3 was a phase 3, double-blind, randomized, placebo-controlled, parallel-group, flexible-dose study that included 507 adults aged 40 to 80 with PD with bradykinesia and motor asymmetry who were using levodopa for at least 4 weeks prior to screening. Participants were randomized 1:1 to receive either tavapadon 5 to 15 mg as a once-daily tablet (n=252) or placebo (n=255). The primary end point of TEMPO-3 was change from baseline in patient-reported (Hauser diary) total good ON time without troublesome dyskinesia.

• The primary end point was met; participants receiving tavapadon experienced an increase of 1.1 hours in daily good ON time without troublesome dyskinesia, relative to placebo (95% CI, 0.6 to 1.7; P<.0001).
• Participants receiving tavapadon also had a significant reduction in daily OFF time: a decrease of 0.94 hours relative to placebo (95% CI, -1.48 to -0.41; P=.0006).
• The safety profile of tavapadon treatment in TEMPO-3 was consistent with previous findings, with most adverse events being mild or moderate in severity.
• Participants receiving tavapadon showed reductions in supine blood pressure and weight.

Tavapadon is an investigative D1/D5 dopamine receptor partial agonist that was previously evaluated as a monotherapy for people with PD at a fixed-dose in the TEMPO-1 clinical trial (NCT04201093) and at a flexible dose in the TEMPO-2 clinical trial (NCT04223193). The primary end point was met in both of these studies: tavapadon monotherapy was associated with statistically significant improvements in Movement Disorder Society – Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score.

A fourth, open-label clinical trial, TEMPO-4 (NCT04760769) is evaluating the long-term 58-week safety and efficacy of tavapadon and is currently ongoing.

Source: Fernandez H, Isaacson S, Hauser R. Efficacy and safety of tavapadon, an orally administered, once-daily, selective d1/d5 partial dopamine agonist, adjunctive to levodopa for treatment of parkinson’s disease with motor fluctuations. Presented at: American Academy of Neurology Annual Meeting; April 5–9, 2025; San Diego, CA.