CHICAGO — An investigational first-in-class oral selective partial D1/D5 dopamine receptor agonist was associated with delayed need for levodopa or dose escalation in patients with Parkinson’s disease (PD), results of a post hoc analysis of the TEMPO-4 trial showed.

After up to 20 months of tavapadon treatment, about 90% of patients with early PD did not require levodopa initiation, and a similar proportion of those with motor fluctuations did not require dose escalation, said study investigator William Ondo, MD, director of the Movement Disorders Clinic at Houston Methodist Neurological Institute in Houston.

The findings were reported April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Evaluating Long-Term Outcomes

Oral levodopa is often needed for symptom control despite known risk for motor complications. In previous trials involving levodopa-naive early PD populations, in which levodopa initiation was allowed, levodopa was started in up to 53% of patients within 12-24 months. 

As previously reported by Medscape Medical News, once-daily oral tavapadon demonstrated significant improvement in motor symptoms across the spectrum of patients with PD in the phase 3 TEMPO-1, TEMPO-2 and TEMPO-3 trials.

To evaluate longer-term outcomes, investigators conducted TEMPO-4, a 58-week open-label extension trial that enrolled patients with PD who had completed the earlier TEMPO trials, along with de novo patients receiving stable levodopa therapy. In total, the study included more than 1000 participants.

Among patients with early PD receiving tavapadon who were levodopa-naive at baseline, most remained off levodopa throughout the study. Between 86% and 94% of patients did not initiate levodopa during the 52-week maintenance phase, and the cumulative probability of initiation remained below 10% for up to 1 year.

Baseline characteristics were generally similar between patients who did and did not initiate levodopa, although those who eventually required it tended to have more severe disease at study entry.

Among patients already receiving levodopa, tavapadon appeared to help stabilize treatment requirements. Most participants, approximately 81%-88%, maintained baseline levodopa dose over the course of the study, and when adjustments were needed, dose reductions were more common than increases.

Cautious Optimism

Commenting on the findings, Michael Okun, MD, medical advisor at the Parkinson’s Foundation, said tavapadon represents “an exciting new therapeutic direction,” noting its selective D1/D5 activity distinguishes it from traditional dopamine agonists.

However, he cautioned against overinterpreting the results.

“We have to be careful of overinterpreting data on using dopamine agonists to delay the need for levodopa while still delivering sustained symptom control. We have been down this road before with agonists and the field was forced to backtrack. Open-label extension studies unfortunately will not provide a definitive answer,” said Okun.

Tavapadon is currently under FDA review as a once-daily oral treatment for PD.

AbbVie funds the TEMPO trials. Disclosure information for study authors is available in the original study publication. Okun is author of the book The Parkinson’s Plan.