CVL-751 · program
Tavapadon for Parkinson's disease
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.
Development timeline
- AbbVie submitted the tavapadon NDA to the U.S. FDA for early and advanced Parkinson's disease.↗
- metTEMPO-2 (flexible-dose monotherapy, early PD) met primary endpoint: -9.1 point treatment difference on MDS-UPDRS II+III (p<0.0001).↗
- metTEMPO-1 (fixed-dose monotherapy, early PD) met primary endpoint at both 5 mg and 15 mg (p<0.0001 vs placebo).↗
- metTEMPO-3 (adjunctive to levodopa, advanced PD) met primary endpoint: +1.1 h additional ON time without troublesome dyskinesia vs placebo (p<0.0001).↗
Readouts
- Sep 2026 (third-party estimate)DelayedRegulatory
FDA decision on tavapadon NDA slipped past 1H 2026; trackers now expect September 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 in Parkinson's disease
NCT04760769TEMPO-4Phase 3Completedn=992
58-Week Open-label Trial of Tavapadon in Parkinson's Disease (TEMPO-4)
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)
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)
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)
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.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| 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) | Oral | Once daily | t½ 24 h · Tmax 3.5 h |
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).
| Target | Action | Affinity |
|---|---|---|
| D1 receptorprimaryDRD1 | Partial agonist | Ki 9 nMⓘ |
| D5 receptorDRD5 | Partial agonist | Ki 13 nMⓘ |
← Full CVL-751 compound page (identity, identifiers, all indications)
Sources
- AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease — AbbVie
- AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease — AbbVie
- AbbVie Completes Acquisition of Cerevel Therapeutics — AbbVie
- AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease — AbbVie
- 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
- FDA Decisions Expected: September 2026 — Prime Therapeutics
- Fixed-Dose Trial in Early Parkinson's Disease (PD) — TEMPO-1 — ClinicalTrials.gov
- Flexible-Dose Trial in Early Parkinson's Disease (PD) (TEMPO-2) — ClinicalTrials.gov
- Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations (TEMPO-3) — ClinicalTrials.gov
- Open-label Trial in Parkinson's Disease (PD) (TEMPO-4) — ClinicalTrials.gov
- Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson's Disease — PMC / peer-reviewed journal
- Tavapadon - Wikipedia — Wikipedia (citing primary receptor-pharmacology literature)