(87) Efficacy and safety of tavapadon, an orally administered, once-daily, selective D1/D5 dopamine agonist, adjunctive to levodopa for treatment of Parkinson’s disease with motor fluctuations

Wednesday, October 29, 2025

Presenter(s)

Hubert H. Fernandez, MD

Professor of Medicine (Neurology)
Center for Neurological Restoration, Cleveland Clinic
Cleveland, Ohio, United States

Primary Author(s)

Hubert H. Fernandez, MD

Professor of Medicine (Neurology)
Center for Neurological Restoration, Cleveland Clinic
Cleveland, Ohio, United States

Co-Author(s)

Stuart H. Isaacson, MD

Director
Parkinson’s Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, United States
Robert A. Hauser, MD

Director, Parkinson's & Movement Disorder Center
University of South Florida, Tampa
Tampa, Florida, United States
Pinky Agarwal, MD, FAAN

Neurologist
Evergreen Health
Kirkland, Washington, United States
William Ondo, MD

Director
Houston Methodist Neurological Institute
Houston, Texas, United States
Ariane Park, MD, MPH

Neurologist
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Lawrence Elmer, MD, PhD

Professor of Neurology
Division of Movement Disorders, Department of Neurology, University of Toledo
Toledo, Ohio, United States
Daniel E. Kremens, MD, JD, FAAN

Co-Director, Movement Disorders Program, Vice Chair of Education in Dept of Neurology
Department of Neurology, Sidney Kimmel Medical College at Jefferson University
Philadelphia, Pennsylvania, United States
Matthew Leoni, MD, MBA

Chief Medical Officer
Merida Biosciences
Cambridge, Massachusetts, United States
Sridhar Duvvuri, PhD

Vice President Clinical Pharmacology and Pharmacometrics
Merida Biosciences
Cambridge, Massachusetts, United States
Cari Combs, MD

Senior Director
AbbVie, at the time of the study
Boston, Massachusetts, United States
Erica Koenig, PhD

Vice President Clinical Development
AbbVie, at the time of the study
East Cambridge, Massachusetts, United States
Ih Chang, PhD

Vice President, Biometrics
AbbVie
Cambridge, Massachusetts, United States
Gina Pastino, PhD, DABT

Senior Director, Clinical Pharmacology
AbbVie
East Cambridge, Massachusetts, United States
Stacey Tringali, PharmD

Head of Clinical Pharmacology and Pharmacometrics
AbbVie, at the time of the study
Cambridge, Massachusetts, United States
Nicole Golonski, MPH

Senior Manager, Clinical Operations at Abbvie
AbbVie, at the time of the study
East Cambridge, Massachusetts, United States
Raymond Sanchez, MD

Senior Advisor
Bain Capital Life Sciences Investors, LLC
Boston, Massachusetts, United States

Background: : Tavapadon is an oral, once-daily selective D1/D5 dopamine agonist. Selective, partial D1/D5 agonism may provide a balance of dopamine signaling that improves Parkinson’s disease (PD) motor symptoms while potentially minimizing certain adverse events (AEs) associated with activation of D2/D3 receptors.

Objective: : To evaluate the efficacy, safety, and tolerability of tavapadon adjunctive to levodopa in adults with PD and motor fluctuations.

Methods: : TEMPO-3 (NCT04542499) is a phase 3, placebo-controlled, double-blind clinical trial evaluating adjunctive therapy with tavapadon in adults experiencing motor fluctuations (modified Hoehn and Yahr stage 2-3 in the ON state, minimum 2.5 h of OFF time on 2 consecutive diary days) while receiving stable levodopa treatment. Participants were randomly assigned (1:1) to receive adjunctive tavapadon (titrated to maximum tolerated flexible dose: 5–15 mg once daily) or placebo. Change from baseline in total daily ON time without troublesome dyskinesia (Hauser diary 2-day average) was the primary endpoint. Key secondary endpoints included change from baseline in total daily OFF time and AEs.

Results: : Adults aged 40-80 years (N=507) were enrolled. Treatment with tavapadon (5–15 mg once daily) significantly increased total daily ON time without troublesome dyskinesia by 1.1 hours relative to placebo (1.7 hours vs 0.6 hours, respectively; P< 0.0001). A significant reduction versus placebo in change from baseline in daily OFF time was also observed. Tavapadon’s safety profile was consistent with prior clinical trials and the majority of AEs were mild to moderate in severity.

Conclusions: : These findings in adults with PD and motor fluctuations demonstrate the efficacy and acceptable safety profile of tavapadon as adjunctive therapy to levodopa. Trials evaluating Tavapadon as a fixed dose (TEMPO-1) and flexible-dose (TEMPO-2) monotherapy in early PD are completed; an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing.

Sponsorship:: AbbVie