Tavapadon Shows Improved Good “On” Time as Add-On Therapy for Parkinson Disease

Adjunctive treatment with investigational tavapadon (AbbVie, North Chicago, IL) increased daily good “on” time and reduced “off” time in adults with Parkinson disease (PD) experiencing motor fluctuations despite stable levodopa therapy, according to phase 3 TEMPO-3 trial (NCT04542499) results published in JAMA Neurology. Tavapadon is an oral, once-daily selective dopamine D1/D5 receptor agonist undergoing evaluation as an alternative adjunctive approach for motor control in PD.

Motor fluctuations are common with long-term levodopa use and can affect activities of daily living and quality of life. The TEMPO-3 investigators evaluated whether adding tavapadon could extend time with good mobility and fewer motor or nonmotor symptoms without increasing troublesome dyskinesia.

Inside TEMPO-3

TEMPO-3 was a phase 3, double-blind, placebo-controlled trial conducted at 148 sites in 14 countries from September 2020 to February 2024. In the study, 507 adults with PD and motor fluctuations were randomized to receive flexible-dose tavapadon 5 to 15 mg once daily or placebo, both added to oral levodopa, for 27 weeks. Participants had a mean age of 64.9 years, mean disease duration of 6.7 years, and mean baseline daily “off” time of 5.5 hours.

Insights from the Study Results

• Tavapadon increased daily “on” time without troublesome dyskinesia by 1.70 hours vs 0.60 hours with placebo at week 26, for a treatment difference of 1.10 hours (95% CI, 0.60 to 1.70; P<.001).
• Daily “off” time decreased by 1.88 hours with tavapadon vs 0.93 hours with placebo, for a treatment difference of −0.94 hours (95% CI, −1.48 to −0.41; P<.001).
• Improvements in good “on” time and “off” time separated from placebo by week 8 and were sustained through week 26.
• Tavapadon was also associated with nominally greater improvements in MDS-UPDRS part II and part III scores, reflecting activities of daily living and motor examination, respectively.

Adverse events occurred in 71.7% of participants receiving tavapadon and 55.1% receiving placebo. Most were mild to moderate. The most common adverse events with tavapadon were nausea (14.3%), dyskinesia (10.0%), dizziness (7.6%), headache (6.8%), falls (6.4%), and orthostatic hypotension (6.0%). Adverse events led to treatment discontinuation in 17.1% of tavapadon-treated participants compared with 9.1% receiving placebo.

The authors noted that TEMPO-3 was not designed to compare tavapadon with existing dopamine agonists or other adjunctive PD therapies, and that longer-term data are needed to further characterize durability and safety.

Sources

Fernandez HH, Isaacson SH, Hauser RA, et al. Tavapadon as Adjunctive Treatment for Parkinson Disease: The TEMPO-3 Randomized Clinical Trial. JAMA Neurol. 2026;83(5):442–451. doi:10.1001/jamaneurol.2026.0577