tavapadon (CVL-751) / AbbVie - LARVOL DELTA

Translational EEG Rat Model of Dyskinesia for Dopaminergic Drug Evaluation in Parkinson's Disease (Neuroscience 2025) - "These findings demonstrate that combining EEG biomarkers with behavioral scoring in our rat model of LID offers a robust platform to evaluate the therapeutic profiles of novel dopaminergic agents. This model is well suited for preclinical screening of compounds with the potential to provide sustained motor benefits while minimizing treatment-emergent dyskinesias, or to de-risk candidates with possible pro-dyskinetic effects before clinical development. Finally, our findings with Tavapadon align with a Parkinsonian non-human primate study (Young et al., ACS Chem."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

A Review of the Recent Advances in the Pharmacological Management of Parkinson's Disease. (PubMed, Cureus) - "There are some limitations to consider with these novel therapies, such as current preclinical or early clinical phases with small sample sizes and follow-up trials. This narrative review aims to provide insight into the existing and emerging pharmacological treatment options for the management of PD, while highlighting the need for innovative strategies to improve outcomes for individuals living with PD, comparing the benefits versus risks."

Journal • Review • CNS Disorders • Gene Therapies • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • COMT

Parkinson Agent Tavapadon Shows Continued Efficacy, Safety in Phase 3 TEMPO-4 Trial (NeurologyLive) - "The interim analysis, presented as a late-breaker at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, included 468 patients who rolled over, and 524 previously untreated participants (placebo rollover: n = 471; de novo; n = 53). Pooling both cohorts (n = 991), the most common treatment-emergent adverse event (TEAE) observed with tavapadon was nausea (11.0%), followed by dizziness (10.6%), headache (9.6%), fall (9.2%), COVID-19 (9.1%), and constipation (5.5%)...Throughout the study, those who stayed on tavapadon continued to show stable motor improvements, while de novo participants and those who crossed over from placebo demonstrated improvements in motor function with continued treatment."

P3 data • Parkinson's Disease

Tavapadon Is Not Associated With Increased Daytime Sleepiness in People With Parkinson's Disease (MDS Congress 2025) - P3 | "Tavapadon is not associated with increased daytime sleepiness compared to placebo when used as monotherapy or adjunctive to levodopa in people with PD. Figure"

CNS Disorders • Excessive Daytime Sleepiness • Movement Disorders • Parkinson's Disease • Sleep Disorder

Changes in Motor States Throughout the Waking Day With Tavapadon in People With Parkinson's Disease (MDS Congress 2025) - P3 | "Objective: To evaluate motor states throughout the waking day when adding tavapadon to oral carbidopa/levodopa in adults with Parkinson's disease experiencing motor fluctuations. Improvement in ON time without troublesome dyskinesia with tavapadon was largely driven by an increase in ON time without dyskinesia and a decrease in OFF time. Figure"

CNS Disorders • Movement Disorders • Parkinson's Disease

TEMPO-4: A Phase 3 Open-Label Trial to Investigate the Safety and Efficacy of Long-term Administration of Tavapadon in People With Parkinson's Disease (MDS Congress 2025) - P3 | "This interim analysis from the TEMPO-4 trial demonstrates that tavapadon has a favorable long-term safety profile and stable efficacy with continued treatment. Low rates of AEs of interest support a potential differentiated approach of selective D1/D5 agonism relative to available dopaminergic therapies."

Clinical • Late-breaking abstract • P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease (AbbVie Press Release) - "The submission is based on results from the TEMPO clinical development program that evaluated the efficacy, safety and tolerability of tavapadon across a broad Parkinson's disease population. This includes two Phase 3 trials (TEMPO-1 and TEMPO-2) in early Parkinson's disease, and one Phase 3 trial (TEMPO-3) with tavapadon as adjunctive to levodopa in patients experiencing motor fluctuations....The submission is also based on an interim data cut from TEMPO-4, an open-label extension (OLE) trial to assess the long-term clinical benefit of tavapadon."

FDA filing • Parkinson's Disease

Emerging Clinical Role of Tavapadon, a Novel Dopamine Partial Agonist, in the Treatment of Parkinson's Disease. (PubMed, Diseases) - "Collectively, evidence indicates that Tavapadon can match levodopa-mediated symptomatic efficacy, lower dyskinesia liability compared with levodopa or earlier full D1 receptor (D1R) agonists, and offer the convenience of once-daily dosing characteristics, which may bridge the therapeutic gap between levodopa and the current D2R/D3R agonists in PD management. In the present investigation, the emerging clinical role for Tavapadon is described, along with the mechanism of action, clinical efficacy, safety, and future directions."

Journal • Review • CNS Disorders • Hypotension • Movement Disorders • Pain • Parkinson's Disease

Expanded Access to Tavapadon (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: AbbVie

New trial • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=83 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=83 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

Orally Bioavailable Dopamine D1/D5 Receptor-Biased Agonists to Study the Role of β-Arrestin in Treatment-Related Dyskinesia in Parkinson's Disease. (PubMed, J Med Chem) - "We compared 24 with tavapadon, which shows weak efficacy for β-arrestin signaling, in a rat model of Parkinson's disease with L-DOPA-induced dyskinesias. At particular doses, compound 24 produced efficacy comparable to L-DOPA, but with fewer concomitant dyskinesias. This first in vivo study suggests that β-arrestin may have a positive influence on reducing dyskinesias following acute administration."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Estimation of Dopamine D1 Receptor Agonist Binding Kinetics Using Time-Resolved Functional Assays: Relation to Agonist-Induced Receptor Internalization by Investigational Antiparkinsonian Therapeutics. (PubMed, ACS Chem Neurosci) - "Tavapadon and apomorphine were partial agonists in both assays, whereas A77636 and dihydrexidine showed efficacies similar to dopamine. While our results do not provide evidence for a direct correlation between agonist dissociation and liability to tolerance induction, the possibility remains that certain combinations of agonist characteristics, such as high efficacy paired with slow dissociation, are associated with tolerance induction by D1R agonists."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • ARRB1

Motor fluctuations in Parkinson disease - a mini-review of emerging drugs. (PubMed, Expert Opin Emerg Drugs) - "Preliminary results of a phase III study of dopamine D1/D5 agonist tavapadon and phase II of CVN424, a GRP6 inverse agonist suggest improved ON time. Negative studies were reported with foliglurax (MGluR4 inverse agonist) and the repurposed drugs naftazone and bumetanide. Several novel targets are in early-stage development with results awaited. Overall, it is unclear whether the field is significantly further ahead, as the benefit of these emerging drugs in comparison with currently available agents for motor fluctuations needs to be clarified."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Characterization of Gαs and Gαolf activation by catechol and non-catechol dopamine D1 receptor agonists. (PubMed, iScience) - "In contrast, the non-catechol agonist tavapadon acted as a full agonist at Gαolf and a partial agonist at Gαs. The effects of these ligands on the thalamocortical and striatonigral electrophysiological events, as well as on the locomotor activity and cognitive function of mice agreed with their selectivity profiles in vitro. These findings suggest the possibility of achieving region-specific pharmacology and open new directions for developing D1R drugs to treat relevant neurological and neuropsychiatric disorders."

Journal • CNS Disorders • Mental Retardation • Psychiatry

Tavapadon as adjunct to levodopa increases daily ON time in Parkinson's disease (Medical Xpress) - P3 | N=507 | TEMPO-3 (NCT04542499) | Sponsor AbbVie | "For patients with Parkinson's disease with motor fluctuations, the oral once-daily, selective D1/D5 partial dopamine agonist tavapadon as an adjunct to levodopa increases total daily ON time versus placebo, according to a study presented at the annual meeting of the American Academy of Neurology, held from April 5 to 9 in San Diego....A total of 507 patients (aged 40 to 80 years) were enrolled and randomly assigned to adjunctive tavapadon...or placebo in a 1:1 ratio. The researchers found that tavapadon treatment significantly increased total daily ON time without troublesome dyskinesia (1.7 hours versus 0.6 hours with placebo). There was also a significant reduction in the change from baseline in daily OFF time compared with placebo. The safety profile of tavapadon was consistent with that seen in previous clinical trials; most adverse events were mild to moderate in severity."

P3 data • Parkinson's Disease

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

Efficacy and Safety of Fixed-Dose Tavapadon, an Oral, Once-Daily, Selective D1/D5 Partial Dopamine Agonist for the Treatment of Early Parkinson's Disease (AAN 2025) - P3 | "Conclusions In 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."

Clinical • Late-breaking abstract • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy and Safety of Flexible-Dose Tavapadon, an Orally Administered, Once-Daily, Selective D1/D5 Partial Dopamine Agonist for the Treatment of Early Parkinson's Disease (AAN 2025) - P3 | "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."

Clinical • Late-breaking abstract • CNS Disorders • Movement Disorders • Parkinson's Disease

Managing impulse control and related behavioral disorders in Parkinson's disease: where we are in 2025? (PubMed, Expert Rev Neurother) - "Insights into ICDs pathophysiology and DA-specific pharmacodynamics indicate safer profiles for certain preparations (e.g. rotigotine patches) and possibly for D1/D5 agonists like tavapadon. Invasive treatments, including deep brain stimulation and infusion therapies, should be prioritized in advanced-stage PD complicated by ICBDs."

Journal • Review • Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry

A Study to Assess the Relative Bioavailability of Oral Tavapadon in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=84 | Not yet recruiting | Sponsor: AbbVie

New P1 trial

Efficacy and Safety of Tavapadon, an Orally Administered, Once-daily, Selective D1/D5 Partial Dopamine Agonist, Adjunctive to Levodopa for Treatment of Parkinson's Disease with Motor Fluctuations (AAN 2025) - P3 | "These findings in adults with PD and motor fluctuations demonstrate the efficacy and acceptable safety profile of tavapadon as adjunctive therapy to levodopa. Tavapadon as monotherapy in early PD (TEMPO-1 and TEMPO-2) and the long-term use of tavapadon (open-label extension; TEMPO-4) are being evaluated in ongoing phase 3 trials."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson’s Disease (PRNewswire) - P3 | N=304 | TEMPO-2 (NCT04223193) | Sponsor: Cerevel Therapeutics, LLC | "AbbVie...today announced positive topline results from its pivotal Phase 3 TEMPO-2 trial evaluating investigational tavapadon as a flexible-dose monotherapy in early Parkinson's disease...The trial met its primary endpoint – patients treated with tavapadon experienced a statistically significant reduction (improvement) from baseline compared to placebo (placebo: -1.2; tavapadon 5-15 mg: -10.3; p-value <0.0001 versus placebo) in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26...Full results from the TEMPO-2 trial will be submitted for presentation at a future medical meeting. AbbVie is on track to submit the New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) in 2025."

FDA filing • P3 data: top line • CNS Disorders • Parkinson's Disease

TEMPO-2: Flexible-Dose Trial in Early Parkinson's Disease (PD) (clinicaltrials.gov) - P3 | N=304 | Completed | Sponsor: Cerevel Therapeutics, LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease