A New Drug Application (NDA) has been submitted to the U.S. Food and Drug Administration (FDA) for tavapadon, a once-daily, oral treatment for the tremors, slowness and stiffness — referred to as motor symptoms — that occur in Parkinson’s disease. One of the last steps in the drug development process, an NDA includes information from clinical trials about the safety and effectiveness of a drug to inform FDA decision making on its approval.
Tavapadon is a dopamine agonist, a class of drugs that bind to dopamine receptors and mimic dopamine’s action in the brain. Dopamine is the brain chemical that decreases in Parkinson’s disease, causing motor symptoms to develop. Unlike other dopamine agonists, tavapadon selectively stimulates only two of the five dopamine receptors in the brain. This more focused action may ease Parkinson’s motor symptoms, potentially without the adverse effects that some other dopamine agonists can cause, such as impulse control disorders (like excessive gambling, spending or overeating), leg swelling or excessive daytime sleepiness. It’s important to note that the new drug has not yet been proven to cause fewer side effects, nor has it been directly compared to other dopamine agonists. The idea of fewer side effects is a theory based on how the medication works.
“It’s encouraging to see continued improvement of dopamine therapies for Parkinson’s,” said Rachel Dolhun, MD, DipABLM, principal medical advisor at The Michael J. Fox Foundation. “Not every treatment works for every person with Parkinson’s or for all of their Parkinson’s. Each new advance is a potential opportunity to manage Parkinson’s symptoms in a different or better way.”
Clinical Trial Results Support NDA
The TEMPO clinical development program includes four Phase III studies — TEMPO-1, TEMPO-2, TEMPO-3 and TEMPO-4 — evaluating the safety, effectiveness and tolerability of tavapadon in a large population of people living with Parkinson’s disease. Data from TEMPO-1, TEMPO-2 and TEMPO-3 contributed to the recent NDA submission; the TEMPO-4 study is ongoing.
TEMPO-1, TEMPO-2, and TEMPO-3 studied tavapadon in men and women between ages 40 and 80, with an average age of early 60s. In TEMPO-1 and TEMPO-2, participants had been diagnosed with Parkinson’s less than three years and had never taken Parkinson’s medication. In TEMPO-3, participants were required to be on a stable dose of levodopa.
Treatment with Tavapadon Alone
Both TEMPO-1 and TEMPO-2 were double-blind, randomized, placebo-controlled clinical trials, the gold standard in medical research. In this type of trial, participants are randomly assigned to either a treatment group, which receives the drug under study, or a control group, which gets either standard treatment (such as levodopa) or a placebo. In a double-blind study, neither the researchers nor the participants know what treatment group they’re in, which is important for reducing potential biases.
In TEMPO-1, researchers compared a group of patients taking either 5 mg or 15 mg of tavapadon to patients who received a placebo. Results showed that compared with the placebo group, volunteers who received tavapadon experienced a significant improvement in motor symptoms and activities of daily living (like speech, dressing, hygiene, and walking) as measured by the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS–UPDRS) Parts II and III, after about six months.
Results from TEMPO-2 were similar: Although this study evaluated a flexible dose of tavapadon — slowly increased from 5 mg daily to 15 mg daily — people who were treated with any dose experienced a significant reduction in both motor symptom scores and a significant improvement in experiences of daily living, compared to people taking placebo, after a similar treatment period as the previous study.
Treatment with Tavapadon Plus Levodopa
In TEMPO-3, researchers evaluated tavapadon as an additional, or adjunctive, treatment to levodopa in people with mild to moderate Parkinson’s disease and motor fluctuations, the ups and downs in symptom control throughout the day. Eligible participants were on a stable dose of levodopa — at least 400 mg per day of standard-release or at least 300 mg per day of extended-release — and maintained that dose for the duration of the trial.
The results showed that compared with people taking levodopa and a placebo, the combination of tavapadon with levodopa gave people an extra 1.1 hours of daily total “on” time — the period when Parkinson’s symptoms are well-controlled — without dyskinesia or other unwanted side effects, and a significant reduction in “off” time, when symptoms return.
Ongoing Studies
Interim results of the ongoing TEMPO-4 study were presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS) Meeting. In this open-label extension study, researchers are evaluating the safety and effectiveness of long-term tavapadon therapy in Parkinson’s. In an open-label extension study, participants from previous clinical trials — in this case, TEMPO-1, TEMPO-2, and TEMPO-3, regardless of whether they received the treatment or placebo — are treated with the study drug for a longer time period to collect data on the longer-term, real-world safety and tolerability of a drug.
Among people who completed more than a year of treatment, tavapadon continued to show that it is generally safe (reported adverse effects included nausea, dizziness, headache, constipation and falls) and effective, with stable, continued motor symptom improvement.
What’s Next for Tavapadon?
If the NDA submission is accepted for review, an update can be expected within 6 to 10 months. If approved, tavapadon would be a new, once-daily oral medication option for people with Parkinson’s — both recently diagnosed and progressing disease. Stay tuned to michaeljfox.org/research-news for the latest or ask your doctor about the latest treatment developments.