The executive medical director at AbbVie discussed the FDA approval of tavapadon, the first D1/D5 dopamine agonist for Parkinson disease, including the supporting TEMPO trial data and safety considerations.
In September 2026, the FDA
In the phase 3 TEMPO-1 (NCT04201093) and TEMPO-2 (NCT04223193) studies, which enrolled patients with early PD, tavapadon significantly improved combined Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III scores at week 26 vs placebo. Specifically in the phase 3 TEMPO-2 trial, findings showed that scores decreased by 10.3 points with tavapadon vs 1.2 points with placebo (difference, –9.1; P <.001).2,3
In the phase 3TEMPO-3 study (NCT04542499), adjunctive tavapadon increased daily ON time without troublesome dyskinesia by 1.1 hours vs placebo in patients with motor fluctuations on levodopa.1,4 In terms of safety, discontinuations because of adverse events (AEs) were more common with tavapadon, most occurring during titration, and the prescribing information includes warnings for orthostatic hypotension, hallucinations, dyskinesia, and impulse control behaviors.1,3
Cindy Zadikoff, MD, MSc: A lot of excitement, of course. As you know, drug development is a journey, and we have been on this journey for a long time. We felt that we had a really good drug when we saw the results of all of our studies, but of course, you still have to go through that process of approval. To finally get it was really a culmination of a lot of hard work from a lot of people, including all the people who participated in our trials. It was wonderful.
I think the beauty of this drug is that it is approved for the treatment of PD, and what that means is it really allows physicians to work with their patients to meet them wherever they are in their treatment journey. For an early patient with PD who is not on levodopa therapy, this could provide an opportunity to potentially delay that step. If they’re on levodopa and needing to consider dose adjustments, this gives them an opportunity to delay that step and, hopefully, avoid some of the AEs that we see with the other drugs as well.
I think whenever drug developers, patients, or physicians see new innovations coming into the market, that brings a lot of optimism. We have drug failures, and it’s hard. Tavapadon is the first novel mechanism to be approved in PD in quite some time. This really helps people recognize that there is potential, there is innovation available, and we can continue to improve upon the treatment paradigms that patients are using today.
There were 3 main trials that supported the approval, as well as the long-term open-label extension. Two of those trials were in patients with early PD who were not on levodopa. An additional trial, TEMPO-3, was in patients on levodopa who were experiencing motor fluctuations.
In those first 2 trials, the primary end point was Parts II and III of the MDS-UPDRS. That includes both the patients’ experience with their day-to-day activities of daily living and the physician’s judgment, using Part III. vs placebo, there was really robust improvement in Parts II and III at week 26, demonstrating that this can improve people’s ability to do their activities of daily living.
The TEMPO-3 study had a different end point that looked at motor fluctuations and the improvement in ON time. Compared with placebo, adding tavapadon to levodopa really did improve people’s ON time, reducing the amount of time that they were OFF, and it did so without worsening troublesome dyskinesias. So again, it really covers that spectrum of the patient journey.
Every physician will look at their patient individually and make treatment choices based on the individual in front of them and their needs. I think they can use the studies to guide them, and there you can see that the benefit was seen across the spectrum. As importantly, there was an absence of many of the AEs that may cause a physician to be reluctant to prescribe certain other medications, like the existing D2/D3 agonists. There wasn’t the somnolence, and there weren’t the sleep attacks that can be so bothersome and really impact a person’s daily life. It’s those 2 things together, that robust efficacy with a good safety and tolerability profile, that will hopefully allow physicians to look at their patients and feel that it is a good fit for them.
Many of the AEs that we saw tend to occur during titration. Some of the things that you see are nausea, dizziness, and headaches. Most of those appear earlier during treatment, and once patients made it to maintenance dosing, many of those did improve.
We’re very excited to bring this to market. It is a novel mechanism. It is the first and only D1/D5 dopamine agonist that is available, and for patients, it is a once-daily therapy. I think the novelty of it, as well as the convenience of it, will hopefully address an unmet need for patients and their prescribers.
Transcript edited for clarity.
