FDA Approves Tavapadon, First D1/D5 Agonist for Parkinson Disease

The FDA has approved tavapadon (Juvmo; AbbVie), an oral, once-daily selective D1/D5 partial agonist, for the treatment of adults with Parkinson disease, according to a news release from AbbVie. The approval gives clinicians a dopamine agonist that works through a different receptor pathway than currently available agents, which primarily target D2/D3 receptors, but a 6-week titration and an extensive CYP3A interaction profile put pharmacists at the center of getting patients started safely.^1,2

AbbVie describes tavapadon as the first and only selective D1/D5 receptor agonist approved for Parkinson disease and expects it to be available in the US in October 2026. The label carries no contraindications.^1,2

Early Parkinson Disease Without Levodopa

The phase 3 TEMPO-1 trial (NCT04201093) randomly assigned 529 adults with early Parkinson disease (less than 3 years' duration) who were treatment naive or had less than 3 months of prior dopaminergic therapy to tavapadon 5 mg, tavapadon 15 mg, or placebo once daily for 27 weeks. At week 26, the combined Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III score decreased by 9.7 points with 5 mg and 10.2 points with 15 mg, compared with a 1.8-point increase with placebo (treatment differences, −11.5 and −12.1 points; P < .001 for both).^3,4

In TEMPO-2 (NCT04223193), 304 participants were randomly assigned to flexible-dose tavapadon 5 to 15 mg or placebo. The combined score fell by 10.3 points with tavapadon versus 1.2 points with placebo (treatment difference, −9.1; P < .0001).^5,6

The prescribing information reports MDS-UPDRS part 2, which captures activities of daily living, as the efficacy end point for both trials. Least-squares mean changes at week 26 were −1.6 (5 mg) and −1.7 (15 mg) vs 0.9 with placebo in TEMPO-1 and −1.5 vs 0.0 in TEMPO-2 (P = .0007).²

Adjunctive Use With Levodopa

TEMPO-3 (NCT04542499) enrolled 507 adults with Parkinson disease and motor fluctuations on a stable levodopa dose of at least 400 mg per day. At week 26, daily "on" time without troublesome dyskinesia increased by 1.7 hours with tavapadon vs 0.6 hours with placebo (P < .0001), and daily "off" time decreased by 1.9 vs 0.9 hours (P = .0006). AbbVie also cited unpublished data from the TEMPO-4 open-label extension indicating that 93% of participants taking tavapadon with levodopa for 85 weeks did not increase their levodopa dose.^1,2

Tolerability and Titration

Nausea, headache, and dizziness were the most common adverse events in both early-disease trials. Adverse events led to discontinuation in 18.1% of participants receiving tavapadon vs 4.0% receiving placebo in TEMPO-1 and in 24% vs 4% in TEMPO-2; per the label, 85% of adverse event–related discontinuations occurred during titration or dose adjustment. Somnolence occurred at rates similar to placebo in TEMPO-1, and impulse control disorders were reported in 0.8% of participants receiving tavapadon.^2,3,5

The label carries warnings for hypotension and orthostatic hypotension, impulse control and compulsive behaviors, hallucinations, and dyskinesia. Hallucinations were reported in 7% of participants receiving tavapadon with levodopa vs 1% with placebo, and risk appears to increase with age; dyskinesia occurred in 10% vs 2%.²

Titration starts at 0.25 mg once daily and advances stepwise to the 5-mg maintenance dose on day 41, with a dedicated titration pack recommended. The dose may be increased in 5-mg increments approximately every 15 days to a maximum of 15 mg once daily. Patients should be counseled to rise slowly from sitting or lying down, particularly during dose escalation.²

Interaction Screening

Tavapadon is a CYP3A substrate. Strong or moderate CYP3A inhibitors should be avoided during titration; for patients on maintenance therapy, the label reduces dosing frequency to once every 7 days with a strong inhibitor and once every 3 days with a moderate inhibitor. Itraconazole increased tavapadon exposure 5-fold, and strong inhibitors may raise hallucination risk. Strong CYP3A inducers are not recommended, while long-term moderate inducers require more frequent dosing. Tavapadon itself induces CYP3A and inhibits CYP2C8 and breast cancer resistance protein (BCRP), which may require dose changes for affected substrates.²

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. Juvmo (tavapadon). Prescribing information. AbbVie Inc; 2026. Accessed September 28, 2026. https://www.rxabbvie.com/pdf/juvmo_pi.pdf

3. 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

4. Fixed-dose trial in early Parkinson's disease (PD) (TEMPO-1). ClinicalTrials.gov Identifier: NCT04201093. Last Updated July 28, 2025. Accessed September 28, 2026. https://clinicaltrials.gov/study/NCT04201093?cond=NCT04201093&rank=1

5. 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

6. Flexible-dose trial in early Parkinson's disease (PD) (TEMPO-2). ClinicalTrials.gov Identifier: NCT04223193. Last Updated November 21, 2025. Accessed September 28, 2026. https://clinicaltrials.gov/study/NCT04223193