TEMPO-2 Data Supports Tavapadon’s Efficacy in Early-Stage Parkinson Disease

Full results from TEMPO-2, a phase 3 trial of the investigational D1/D5 partial agonist tavapadon (AbbVie) in early Parkinson disease (PD), have been published in Lancet Neurology.¹ The trial's topline results were first reported by AbbVie in December 2024, and its findings now form part of the evidence base behind the drug's pending FDA application.^1,2

Trial design

TEMPO-2 (NCT04223193) enrolled 304 adults aged 40 to 80 years with early-stage PD, defined as disease duration under 3 years, who were either treatment-naive or had less than 3 months of prior dopaminergic treatment. Participants were randomized 1:1 to flexible-dose tavapadon (5-15 mg once daily) or placebo for 27 weeks, with the primary endpoint measuring change from baseline to week 26 on the combined Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III score.¹

TEMPO-2 was designed alongside a companion trial, TEMPO-1, which tested tavapadon at 2 fixed doses (5 mg and 15 mg) rather than a flexible dose. Cindy Zadikoff, MD, MSc, senior medical director of clinical development in neuroscience at AbbVie and a TEMPO-2 co-author, explained the distinction in an interview.

“When you're first starting the studies, you're not quite sure...what are the doses in real world, or I guess in trial world, that are going to work but also wanting to make sure you have safety coverage to cover that higher end of the spectrum,” Zadikoff said. She noted that despite the "flexible dose" label, the protocol required most participants to titrate to the full 15 mg dose unless they couldn't tolerate it. “It was not designed in such a way that you could stop at 5 or 10 if you wanted to,” she said. “That really was done to make sure we were getting enough exposures at that highest dose level.”

Efficacy results

The primary endpoint was met: tavapadon produced a least-squares mean decrease of 10.3 points on the combined MDS-Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III score at week 26, compared with 1.2 points with placebo, a treatment difference of 9.1 points (95% CI, -11.7 to -6.5; P < .0001). Improvement was apparent as early as week 5 and continued through the end of treatment.¹

Tavapadon also produced significant improvement on the MDS-UPDRS Part II score alone (treatment difference, -1.5; P = .0007), and a significantly higher proportion of tavapadon-treated patients reported being "much improved" or "very much improved" on the Patient Global Impression of Change scale (46% vs 19%; P < .0001).

Zadikoff pointed to the consistency across the broader TEMPO program as a key takeaway. “If you look at the data between TEMPO-1 and TEMPO-2, they really are very, very consistent across the board when we look at everything, all of the primary and the secondary endpoints, as well as the safety profile,” she said. She added that the benefit wasn't limited to physician-rated assessments: “It is not just driven by just what the physician is saying, it is driven as well by that Part 2, so really the patient experience robust results as well, and it is also complemented by the PGICs...which were also very robust.”

Safety results

In terms of safety, more adverse events (AEs) occurred with tavapadon than placebo (76% vs 55%), and discontinuation due to AEs was more common with tavapadon (24% vs 4%), with most adverse events and discontinuations concentrated in the titration phase rather than during maintenance. The most common AEs with tavapadon were nausea (30%), headache (17%), and dizziness (16%). Rates of somnolence (3% vs 4%) and impulse control disorders (1% vs 0%) were low and similar to placebo, and no dyskinesia was reported in either group.¹

“We didn't see really much in the way of ICDs or peripheral edema, things that we know have plagued the use of the D2/D3 agonists,” Zadikoff said. “The other thing that we did see is that the rates of somnolence were very, very low...again, very consistent with what we've seen in TEMPO-1 and TEMPO-3. Again, the consistency helps you really believe that, and potentially points to that differentiated mechanism of D1/D5 versus D2/D3.”

Regulatory path

TEMPO-2 is one of 3 pivotal phase 3 trials, alongside TEMPO-1 and the adjunctive TEMPO-3 trial, supporting AbbVie's NDA for tavapadon, which the company submitted to the FDA in September 2025.³ An ongoing open-label extension trial, TEMPO-4, is collecting longer-term safety and efficacy data.¹

Asked what approval could mean for the PD community, Zadikoff pointed to differentiated mechanism and choice. "It's always nice to have choice, both for patients and providers," she said. "There really isn't a D1/D5 agonist out there, so something that can provide the motor efficacy without having to sacrifice some of those tolerability issues that have plagued some of the D2/D3s...it could play a role both in that early patient population prior to starting something like levodopa therapy. It can also play a role in people when they're looking to make a change, when they're on levodopa and need additional therapy as well.”

REFERENCES
1. 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)00XXX-X
2. AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease. News release. AbbVie. December 9, 2024. Accessed August 18, 2026. https://news.abbvie.com/2024-12-09-AbbVie-Announces-Positive-Topline-Results-for-the-Phase-3-TEMPO-2-Trial-Evaluating-Tavapadon-as-a-Monotherapy-for-Parkinsons-Disease
3. AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease. News release. AbbVie. September 26, 2025. Accessed August 18, 2026. http://news.abbvie.com/2025-09-26-AbbVie-Submits-New-Drug-Application-to-U-S-FDA-for-Tavapadon-for-the-Treatment-of-Parkinsons-Disease