FDA Approves Tavapadon for the Treatment of Parkinson Disease

The FDA has approved tavapadon (AbbVie), a once-daily oral selective dopamine D1/D5 receptor partial agonist, for adults with Parkinson disease (PD). Marketed as Juvmo, it is the first approved dopamine agonist that selectively targets the D1-like receptor family rather than D2/D3 receptors and can be taken with or without levodopa.¹

The approval is based on the phase 3 TEMPO program, which evaluated tavapadon as monotherapy in early PD and as an adjunct to levodopa in patients with motor fluctuations.^1-4 “What makes tavapadon unique is its D1 selectivity. We can stimulate motor pathways effectively, but the hope is to avoid the baggage that comes with D2 stimulation, particularly the nonmotor side effects," global principal TEMPO trial investigator Hubert Fernandez, MD, a professor of neurology at Cleveland Clinic Lerner College of Medicine, told NeurologyLive^® in a recent interview.¹ AbbVie expects tavapadon to be available in the US in October 2026.

TEMPO Program Results

TEMPO-1 (NCT04201093) randomly assigned 529 adults to fixed-dose tavapadon 5 mg, 15 mg, or placebo for 27 weeks. Participants had PD of less than 3 years' duration and were either treatment naive or had received less than 3 months of dopaminergic therapy.² At week 26, the combined Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III score changed by –9.7 points with the 5-mg dose and –10.2 points with the 15-mg dose, vs +1.8 points with placebo (P <.001 for each).^1,2 Part II scores, which reflect motor aspects of daily living, also improved significantly with both doses.

In TEMPO-2 (NCT04223193), 304 patients with early PD were randomly assigned 1:1 to flexible-dose tavapadon (5-15 mg) or placebo. The combined Parts II and III score decreased by 10.3 points with tavapadon vs 1.2 points with placebo (difference, –9.1; 95% CI, –11.7 to –6.5; P <.001).³

READ MORE: EU Approves Modified-Release Carbidopa/Levodopa Capsules for Parkinson Disease Motor Fluctuations

TEMPO-3 (NCT04542499) enrolled 507 adults with motor fluctuations on stable levodopa of at least 400 mg daily. Adjunctive tavapadon increased daily ON"time without troublesome dyskinesia by 1.7 hours vs 0.6 hours with placebo (difference, 1.1 hours; 95% CI, 0.6-1.7; P <.001). It also reduced OFF time by 1.9 hours vs 0.9 hours.^1,4

Most treatment-emergent adverse events (TEAEs) were mild or moderate. As monotherapy, the most common TEAEs (≥ 5%) were nausea, headache, dizziness, fatigue, dysgeusia, vomiting, dry mouth, and anxiety. With levodopa, they included nausea, dyskinesia, dizziness, headache, hallucinations, and orthostatic hypotension. In TEMPO-2, AEs occurred in 76% of tavapadon-treated patients vs 55% with placebo. Discontinuations because of AEs were 24% vs 4%, and most occurred during titration.³ The prescribing information includes warnings for orthostatic hypotension, hallucinations, dyskinesia, and impulse control behaviors such as compulsive gambling and shopping.¹

Clinical Context and Mechanism

Levodopa remains the foundation of PD treatment, but dose escalation can contribute to motor complications including dyskinesia. AbbVie cites internal data indicating that roughly 70% of patients have their levodopa dose increased within the first year.¹ Currently available dopamine agonists act primarily at D2/D3 receptors, and tolerability often limits their use.^1,2 Tavapadon was designed on the premise that selective, partial D1/D5 agonism could improve motor symptoms while minimizing adverse events associated with D2/D3 activation.^2,4

Interpreting the Data

The TEMPO trials consistently showed efficacy against placebo in both early and fluctuating PD, but none compared tavapadon directly with levodopa or with D2/D3 agonists. As the TEMPO-3 investigators noted, the program was not designed to establish relative efficacy or tolerability vs existing therapies, so claims of a differentiated safety profile should be read in that light.⁴ Titration-phase discontinuations were notable, and the impulse control warnings mirror those for the drug class.^1,3

Longer-term evidence comes from TEMPO-4, an open-label extension. AbbVie reported that after 85 weeks, 93% of participants on adjunctive tavapadon (96/103) had not increased their levodopa dose, and 94% on monotherapy (257/273) had not started levodopa. These figures come from company data on file, lack a control arm, and include only patients who remained on treatment. Open questions include how tavapadon performs in patients older than 80 years, who were excluded from the pivotal trials, and how it compares with other therapies in real-world use.^2,4

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REFERENCES
1. U.S. FDA approves AbbVie's JUVMO (tavapadon) for Parkinson's disease. News release. AbbVie. September 28, 2026. Accessed September 28, 2026. https://news.abbvie.com/2026-09-28-U-S-FDA-Approves-AbbVies-JUVMO-TM-tavapadon-for-Parkinsons-Disease
2. Pahwa R, Moro E, Espay AJ, et al. Fixed-dose tavapadon for early Parkinson disease: a randomized clinical trial. JAMA Neurol. 2026;83(5):452-460. doi:10.1001/jamaneurol.2026.0590
3. Fernandez HH, Bhatia P, Cloud L, et al. Safety, tolerability, and efficacy of flexible-dose tavapadon for Parkinson's disease (TEMPO-2): a phase 3, randomised, placebo-controlled, double-blind trial. Lancet Neurol. 2026;25(8):721-730. doi:10.1016/S1474-4422(26)00215-2
4. Fernandez HH, Isaacson SH, Hauser RA, et al. Tavapadon as adjunctive treatment for Parkinson disease: the TEMPO-3 randomized clinical trial. JAMA Neurol. 2026;83(5):442-451. doi:10.1001/jamaneurol.2026.0577