FDA approves tavapadon, the first selective D1/D5 receptor agonist, for Parkinson’s disease

On September 28, 2026, the U.S. Food and Drug Administration (FDA) approved tavapadon tablets for the treatment of Parkinson’s disease (PD) in adults. Tavapadon is the first selective dopamine D1/D5 receptor agonist approved for PD and can be taken once daily, with or without levodopa therapy. The approval was supported by data from the Phase III TEMPO clinical trial program, demonstrating improvements in activities of daily living, daily “on” time without troublesome dyskinesia, and a favorable safety profile.¹

Unmet need in Parkinson’s disease

PD is a progressive neurological disorder characterized by motor symptoms including tremor, muscle rigidity, slowness of movement, and difficulties with balance. More than 11 million people worldwide are living with PD. As the disease progresses, people may experience motor and non-motor fluctuations and dyskinesia, with symptoms fluctuating between “on” periods, when symptoms are generally well controlled, and “off” periods, when symptoms such as tremor and stiffness may return.¹

Oral levodopa remains a foundation of PD treatment and can provide effective symptom control. However, many patients require higher and more frequent doses over time, which may contribute to treatment-related complications such as dyskinesia.¹ Dopamine agonists have also been used to manage motor symptoms and reduce reliance on increasing doses of oral levodopa. Currently available dopamine agonists primarily target D2/D3 receptors, while tavapadon selectively targets D1/D5 receptors, providing a different approach to dopaminergic treatment.¹

Pivotal data: the Phase III TEMPO program

The FDA approval was supported by data from the Phase III TEMPO program, which evaluated tavapadon in people with early PD who were not receiving oral levodopa in TEMPO-1 (NCT04201093) and TEMPO-2 (NCT04223193), and as an adjunctive treatment to oral levodopa in people experiencing motor fluctuations in TEMPO-3 (NCT04542499).¹

In the Phase III, double-blind, placebo-controlled TEMPO-1 and TEMPO-2 trials, tavapadon was evaluated in adults with early PD who were treatment-naive or had received less than 3 months of previous dopaminergic treatment.^2,3 TEMPO-1 randomized 529 participants across 102 sites in 12 countries to fixed-dose tavapadon 5 mg, tavapadon 15 mg, or placebo once daily for 27 weeks.² TEMPO-2 randomized 304 participants across 75 sites in 13 countries to flexible-dose tavapadon 5–15 mg once daily or placebo for 27 weeks.³ The primary endpoint of both trials was the change from baseline to week 26 in Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III combined score, assessing activities of daily living and motor function.^2,3

At week 26, both trials demonstrated significant improvements in the MDS-UPDRS Parts II and III combined score.^2,3 In TEMPO-1, the score decreased by 9.7 points with tavapadon 5 mg and 10.2 points with 15 mg, compared with a 1.8-point increase with placebo (p<0.001 for both doses).² In TEMPO-2, the score decreased by 10.3 points with flexible-dose tavapadon compared with 1.2 points with placebo (treatment difference, −9.1 points; p<0.0001).³ Most adverse events (AEs) were nonserious and mild to moderate in severity. The most commonly reported AEs with tavapadon were nausea, headache, and dizziness.^2,3

TEMPO-3 evaluated tavapadon as an adjunct to oral levodopa in adults with PD experiencing motor fluctuations. The Phase III, double-blind, placebo-controlled trial enrolled 507 participants across 148 sites in 14 countries. Participants had PD with motor fluctuations while receiving stable oral levodopa at a dose of at least 400 mg daily and were randomized to flexible-dose tavapadon 5–15 mg once daily or placebo for 27 weeks.The primary endpoint was change from baseline to week 26 in total daily “on” time without troublesome dyskinesia.⁴

At week 26, tavapadon significantly increased daily good-on-time by 1.10 hours compared with placebo (1.70 vs 0.60 hours; 95% CI, 0.60-1.70; p<0.001). Tavapadon also significantly reduced daily “off” time, with a reduction of 1.88 hours compared with 0.93 hours with placebo (difference, −0.94 hours; p<0.001). The safety findings from TEMPO-3 were generally favorable. Treatment-emergent AEs occurred in 71.7% of participants receiving tavapadon compared with 55.1% receiving placebo, although most AEs were nonserious and mild to moderate in severity. The most common AEs with tavapadon were nausea (14.3%), dyskinesia (10.0%), and dizziness (7.6%).⁴

Sustained efficacy was also observed through 85 weeks among participants who continued into the open-label extension study, TEMPO-4 (NCT04760769). After 85 weeks, 93% of participants receiving tavapadon with oral levodopa had not increased their oral levodopa dose, while 94% of participants receiving tavapadon without levodopa had not initiated oral levodopa.¹

Clinical implications

“For many years we thought that dopamine agonists would be effective only if they acted on the dopamine D2 receptor subgroup. But in recent years we have learned that also D1 is very important in Parkinson’s functionality and mobility. Tavapadon is the first D1 agonist that comes to clinical use.” – Angelo Antonini, MD, PhD, University of Padua, Padua, Italy.

The approval of tavapadon introduces a new pharmacological approach to the treatment of PD. By improving motor function and activities of daily living in people with early PD, and increasing daily “on” time while reducing “off” time in people receiving levodopa, tavapadon may help address some of the challenges associated with maintaining symptom control as the disease progresses. Tavapadon is expected to become available to patients in the US in October 2026.¹

Written by Hannah Elkheir

Reviewed by Simon Ng

References

1. AbbVie. U.S. FDA Approves AbbVie’s JUVMO™ (tavapadon) for Parkinson’s Disease. Available here. (Last accessed: 09/30/2026).
2. Pahwa R, Moro E, Espay AJ, et al. Fixed-dose tavapadon for early Parkinson disease: a randomized clinical trial. JAMA Neurol. 2026;83(5):452–460.
3. Fernandez HH, Bhatia P, Cloud L, et al. Safety, tolerability, and efficacy of flexible-dose tavapadon for Parkinson’s disease (TEMPO-2): a phase 3, randomised, placebo-controlled, double-blind trial. Lancet Neurol. 2026;25(8):721–730.
4. 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.