Small Molecule · CVL-751

Tavapadon

Filed (NDA)Cerevel Therapeutics Holdings, Inc.

Oral, once-daily, highly selective dopamine D1/D5 receptor partial agonist with a non-catechol chemical structure, in development for Parkinson's disease as both monotherapy in early PD and adjunctive therapy to levodopa in advanced PD with motor fluctuations.

Also known as: CVL-751, PF-06649751, tavapadon, 1643489-24-0

Data current as of

Modality
Small molecule
Chemical class
pyrimidine-2,4-dione, diaryl ether, trifluoromethylpyridine
Chemistry
Single enantiomer
Mechanism
D1 receptor Partial agonist
Highest phase
Filed (NDA)
Lead indication
Parkinson's disease
Developer
Cerevel Therapeutics Holdings, Inc.
Trials
4 tracked · 416 sites
Next catalyst
FDA decision expected 1H 2026 — Regulatory (Parkinson's disease)

Mechanism of action

Highly selective, oral dopamine D1/D5 receptor partial agonist. Partial agonism (rather than full agonism) at D1/D5 is intended to deliver motor benefit while limiting dyskinesia and the tachyphylaxis seen with full D1 agonists. Non-catechol scaffold with biased Gs-coupled signaling and minimal D1 receptor internalization. No clinically meaningful activity at D2-like receptors (D2/D3/D4 Ki >=4,870 nM).

TargetActionAffinity
D1 receptorprimaryDRD1Partial agonistKi 9 nMⓘ
D5 receptorDRD5Partial agonistKi 13 nMⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Tavapadon oral tablet
5-15 mg once daily (Phase 3 TEMPO program: fixed 5 mg or 15 mg in TEMPO-1; flexible 5-15 mg in TEMPO-2/TEMPO-3)
OralOnce dailyt½ 24 h · Tmax 3.5 h

Development timeline

Filed (NDA)Sept 2025 – Jun 2026
  1. UpcomingFDA decision on the tavapadon NDA anticipated in the first half of 2026.↗
  2. AbbVie submitted the tavapadon NDA to the U.S. FDA for early and advanced Parkinson's disease.↗
Phase 3Apr 2024 – Dec 2024
  1. metTEMPO-2 (flexible-dose monotherapy, early PD) met primary endpoint: -9.1 point treatment difference on MDS-UPDRS II+III (p<0.0001).↗
  2. metTEMPO-1 (fixed-dose monotherapy, early PD) met primary endpoint at both 5 mg and 15 mg (p<0.0001 vs placebo).↗
  3. metTEMPO-3 (adjunctive to levodopa, advanced PD) met primary endpoint: +1.1 h additional ON time without troublesome dyskinesia vs placebo (p<0.0001).↗

Tavapadon for Parkinson's disease

Filed (NDA)ActiveParkinson's disease indication →

AbbVie submitted a New Drug Application to the U.S. FDA on 2025-09-26 for tavapadon across the Parkinson's disease spectrum: monotherapy in early PD and adjunctive therapy to levodopa in advanced PD with motor fluctuations. Filing is supported by the Phase 3 TEMPO program (TEMPO-1, TEMPO-2 monotherapy; TEMPO-3 adjunctive; TEMPO-4 open-label extension), all of which met their endpoints. No public Fast Track/Breakthrough/orphan designation identified, so designations left empty.

Readouts

  • FDA decision expected 1H 2026AnticipatedRegulatory

    FDA decision on the tavapadon NDA anticipated in the first half of 2026. ↗

  • 2025-09-26ReportedRegulatory

    AbbVie submitted the tavapadon NDA to the U.S. FDA for early and advanced Parkinson's disease. ↗

  • 2024-12-09ReportedTopline datametNCT04223193

    TEMPO-2 (flexible-dose monotherapy, early PD) met primary endpoint: -9.1 point treatment difference on MDS-UPDRS II+III (p<0.0001). ↗

  • 2024-09-26ReportedTopline datametNCT04201093

    TEMPO-1 (fixed-dose monotherapy, early PD) met primary endpoint at both 5 mg and 15 mg (p<0.0001 vs placebo). ↗

  • 2024-04-18ReportedTopline datametNCT04542499

    TEMPO-3 (adjunctive to levodopa, advanced PD) met primary endpoint: +1.1 h additional ON time without troublesome dyskinesia vs placebo (p<0.0001). ↗

Clinical trials

NCT04760769TEMPO-4Phase 3Completedn=992

58-Week Open-label Trial of Tavapadon in Parkinson's Disease (TEMPO-4)

Started Feb 2021· Primary completion Dec 2025· 📍 140 sites across 14 countries (United States, Poland, Spain, Italy)

NCT04542499TEMPO-3Phase 3Completedn=507

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon as Adjunctive Therapy for Parkinson's Disease in Levodopa-Treated Adults With Motor Fluctuations (TEMPO-3)

Started Sept 2020· Primary completion Jan 2024· 📍 146 sites across 14 countries (United States, Poland, Germany, Spain)

metprimaryChange from baseline in total ON time without troublesome dyskinesia at Week 26 (Hauser diary) — +1.1 h vs placebo (tavapadon +1.7 h vs placebo +0.6 h) (<0.0001)

Adjunctive to levodopa in advanced PD with motor fluctuations, tavapadon (5-15 mg QD) increased total ON time without troublesome dyskinesia by a least-squares mean 1.721 h vs 0.619 h for placebo (treatment difference ~1.1 h, p<0.0001).

NCT04223193TEMPO-2Phase 3Completedn=304

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon in Early Parkinson's Disease (TEMPO-2)

Started Jan 2020· Primary completion Oct 2024· 📍 53 sites across 13 countries (United States, Poland, Italy, Germany)

metprimaryChange from baseline in MDS-UPDRS Parts II + III combined score at Week 26 — -9.1 points (95% CI -11.7 to -6.5) (<0.0001)

Flexible-dose (5-15 mg QD) monotherapy met the primary endpoint: tavapadon -10.3 vs placebo -1.2, treatment difference -9.1 points (p<0.0001).

NCT04201093TEMPO-1Phase 3Completedn=529

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses of Tavapadon in Early Parkinson's Disease (TEMPO-1)

Started Dec 2019· Primary completion Jun 2024· 📍 77 sites across 12 countries (United States, Spain, Bulgaria, Germany)

metprimaryChange from baseline in MDS-UPDRS Parts II + III combined score at Week 26 (<0.0001)

Both fixed doses met the primary endpoint: placebo +1.8, tavapadon 5 mg -9.7, tavapadon 15 mg -10.2 (p<0.0001 each dose vs placebo). Fixed-dose monotherapy in early PD.

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More from Cerevel Therapeutics Holdings, Inc.

Identifiers

Sources

  1. AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease — AbbVie
  2. AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease — AbbVie
  3. AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease — AbbVie
  4. Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson's Disease (TEMPO-3) — Cerevel Therapeutics / AbbVie
  5. Fixed-Dose Trial in Early Parkinson's Disease (PD) — TEMPO-1 — ClinicalTrials.gov
  6. Flexible-Dose Trial in Early Parkinson's Disease (PD) (TEMPO-2) — ClinicalTrials.gov
  7. Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations (TEMPO-3) — ClinicalTrials.gov
  8. Open-label Trial in Parkinson's Disease (PD) (TEMPO-4) — ClinicalTrials.gov
  9. Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson's Disease — PMC / peer-reviewed journal
  10. Tavapadon - Wikipedia — Wikipedia (citing primary receptor-pharmacology literature)