(85) Efficacy and safety of fixed-dose tavapadon, an oral, once-daily, selective D1/D5 dopamine agonist for the treatment of early Parkinson’s disease

Wednesday, October 29, 2025

Presenter(s)

Rajesh Pahwa, MD

Professor of Neurology
University of Kansas Medical Center
Kansas City, Kansas, United States

Primary Author(s)

Rajesh Pahwa, MD

Professor of Neurology
University of Kansas Medical Center
Kansas City, Kansas, United States

Co-Author(s)

Elena Moro, MD, PhD

Professor of Neurology
Grenoble Alpes University, CHU of Grenoble, Grenoble Institute of Neuroscience
Grenoble, Rhone-Alpes, France
Alberto Espay, MD, MSc

Professor of Neurology
James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati
Cincinnati, Ohio, United States
Andrew Evans, MBBS, MD, FRACP

Consultant Neurologist
The Royal Melbourne Hospital
Parkville, Victoria, Australia
Angelo Antonini, MD, PhD

Professor – Department of Neuroscience
Parkinson and Movement Disorders Unit, Department of Neuroscience, University of Padova
Padova, Veneto, Italy
Marie Saint Hilaire, MD, FRCP(C), FAAN

Professor of Neurology, Medical Director
Chobanian and Avedisian School of Medicine at Boston University
Boston, Massachusetts, United States
Diego Torres-Russotto, MD

Chair of Neurology and the Distinguished Endowed Chai
Baptist Health Miami Neuroscience Institute, Florida International University
Miami, Florida, United States
Raymond Sanchez, MD

Senior Advisor
Bain Capital Life Sciences Investors, LLC
Boston, Massachusetts, 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
Ih Chang, PhD

Vice President, Biometrics
AbbVie
Cambridge, Massachusetts, United States
Stacey Tringali, PharmD

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

Background: : Tavapadon is an oral, once-daily, selective D1/D5 dopamine agonist that may improve Parkinson’s disease (PD) motor symptoms while potentially minimizing adverse events (AEs) associated with D2/D3 receptor activation.

Objective: : To evaluate the efficacy, safety, and tolerability of fixed-dose tavapadon in adults with early PD.

Methods: : TEMPO-1 (NCT04201093) is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, 27-week trial evaluating 2 fixed doses of tavapadon as monotherapy for adults with early PD (aged 40-80 years; modified Hoehn and Yahr stage 1-2; disease duration from diagnosis < 3 years). Participants were randomly assigned (1:1:1) to receive placebo, 5-mg tavapadon, or 15-mg tavapadon (once daily, titrated to dose) for 27 weeks. Change from baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II+III combined score was the primary endpoint. The MDS-UPDRS

Results: : 529 adults were enrolled; key participant demographics and baseline disease characteristics were balanced across groups and consistent with the target population. Change from baseline in the MDS-UPDRS Parts II+III combined score was significantly reduced in participants treated with 5-mg (-11.5; 95% CI: -13.8, -9.2) and 15-mg tavapadon (-12.1; 95% CI: -14.4, -9.8) compared with placebo (both P< 0.0001). Tavapadon reduced the MDS-UPDRS Part II score versus placebo (5 mg: -2.5, 95% CI: -3.3, -1.7; 15 mg: -2.6, 95% CI: -3.4, -1.7; both P< 0.0001). Safety data demonstrated a profile consistent with prior tavapadon trials; most AEs were non-serious and mild to moderate in severity.

Conclusions: : n individuals with early PD, tavapadon as monotherapy was effective with an acceptable safety profile. Other trials evaluating tavapadon as flexible-dose monotherapy (TEMPO-2) or adjunctive therapy (TEMPO-3) are completed, and an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing.

Sponsorship:: AbbVie