(86) Efficacy and safety of flexible-dose tavapadon, an orally administered, once-daily, selective D1/D5 dopamine agonist for the treatment of early Parkinson’s disease

Wednesday, October 29, 2025

Primary Author(s)

Hubert H. Fernandez, MD

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

Co-Author(s)

Perminder Bhatia, MD

Director
Neuro Pain Medical Center
Fresno, California, United States
Leslie Cloud, MD

Professor and Rogliano Family Endowed Chair, Director
VCU Parkinson’s Disease and Movement Disorders Center
Henrico, Virginia, United States
Urban M. Fietzek, MD

Senior Researcher
Department of Neurology, University Hospital, LMU Munich
München, Bayern, Germany
Michele Matarazzo, MD

Neurologist
HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales
Madrid, La Rioja, Spain
Eric Molho, MD

Neurologist
Albany Medical College
Albany,, New York, United States
Elizabeth Peckham, DO

Neurologists
Central Texas Neurology Consultants
Round Rock, Texas, United States
Arjun Tarakad, MD

Assistant Professor
Baylor College of Medicine
Houston, Texas, United States
Cari Combs, MD

Senior Director
AbbVie, at the time of the study
Boston, Massachusetts, United States
Matthew Leoni, MD, MBA

Chief Medical Officer
Merida Biosciences
Cambridge, 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
Joey Boiser, MD

Medical Director, Medical Safety Evaluation
AbbVie
East Cambridge, Massachusetts, United States
Cindy Zadikoff, MD

Senior Medical Director
AbbVie
East Cambridge, Massachusetts, United States

Presenter(s)

Cindy Zadikoff, MD

Senior Medical Director
AbbVie
East Cambridge, Massachusetts, United States

Co-Author(s)

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 agonism at D1/D5 receptors may provide a balance of dopamine signaling that improves motor symptoms in Parkinson’s disease (PD) while potentially minimizing specific adverse events (AEs) associated with activation of D2/D3 receptors.

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

Methods: : TEMPO-2 (NCT04223193) is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, 27-week trial evaluating flexible-dose tavapadon as monotherapy for adults with early PD (aged 40-80 years; modified Hoehn and Yahr stage 1-2; Movement Disorder Society-Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] Part II score ≥3 and Part III score ≥10). Participants were randomized (1:1) to receive placebo or tavapadon (5-15 mg once daily; titrated to maximum tolerated dose) for 27 weeks. The primary endpoint was change from baseline in MDS-UPDRS Parts II+III combined score. Key secondary endpoints included change from baseline in MDS-UPDRS Part II score and AEs.

Results: : 304 adults were enrolled; key participant demographics and baseline disease characteristics were consistent with the target population and balanced across treatment arms. Tavapadon showed a significant improvement in MDS-UPDRS Parts II+III combined score compared with placebo (least squares mean [LSM] difference, -9.1, 95% CI: -11.7, -6.5; P< 0.0001). MDS-UPDRS Part II score was also significantly improved in the tavapadon versus placebo cohorts (LSM difference, -1.5, 95% CI: -2.4, -0.6; P=0.0007). Safety data showed a profile consistent with prior tavapadon trials; most AEs were non-serious and mild to moderate in severity.

Conclusions: : TEMPO-2 results demonstrate the efficacy and acceptable safety profile of flexible-dose tavapadon as monotherapy in adults with early PD. Trials evaluating tavapadon as fixed-dose monotherapy (TEMPO-1) or adjunctive therapy (TEMPO-3) are completed; an open-label extension trial evaluating long-term use of tavapadon (TEMPO-4) is ongoing.

Sponsorship:: AbbVie