TEMPO trials: Fixed, flexible doses of tavapadon improve motor function in Parkinson’s

Key takeaways:

• In TEMPO-1, fixed 5 mg and 15 mg doses of tavapadon improved outcomes in patients with Parkinson’s disease.
• TEMPO-2 showed that a flexible dose was also associated with significant improvements.

SAN DIEGO — Fixed and flexible doses of tavapadon significantly improved motor function compared with placebo in patients with Parkinson’s disease, according to a pair of phase 3 trials presented at the American Academy of Neurology annual meeting.

Tavapadon (Abbvie), examined in two trials called TEMPO-1 and TEMPO-2, is a once-daily, selective D1/D5 dopamine receptor agonist that is being developed as a potentially safer alternative to D2/D3 receptor agonists.

“A key unmet need in Parkinson’s disease is finding a treatment modality that can balance the good effects of dopamine stimulation while still reducing the dopaminergic side effects,” especially those associated with D2/D3 agonism, Hubert H. Fernandez, MD, the James and Constance Brown Endowed Chair in Movement Disorders, professor of neurology and director of the Center for Neurological Restoration at Cleveland Clinic, said in the late-breaking session.

TEMPO-1: Fixed doses

For the TEMPO-1 trial, Rajesh Pahwa, MD, FAAN, Laverne and Joyce Rider Professor of Neurology at the University of Kansas School of Medicine and director of the Movement Disorder Program at the University of Kansas Health System, and colleagues randomly assigned 529 newly diagnosed, treatment-naive patients to receive 5 mg tavapadon (n = 177), 15 mg tavapadon (n = 177) or placebo (n = 175). The primary endpoint was the change from baseline in a combined score of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III.

The mean age of participants was 63.7 years, and the mean time from diagnosis was less than 1 year.

Pahwa and colleagues examined the efficacy of tavapadon in a modified intention-to-treat (mITT) population, which included 174 participants in the 5 mg group, 172 in the 15 mg group and 174 in the placebo group.

Overall, 129 participants discontinued the trial.

In the mITT population, tavapadon was associated with a significant reduction in the MDS-UPDRS Parts II and III combined score compared with placebo at week 26. Specifically, there was a 9.7-point decrease with the 5 mg dose, 10.2-point decrease with the 15 mg dose and a 1.8-point increase with placebo.

Pahwa said the benefits of tavapadon started as early as week 4 and were maintained throughout the trial.

Most of the adverse events were not serious, Pahwa said. The most common treatment-emergent adverse events (TEAEs) were nausea, dizziness and headache.

The incidence of treatment-related TEAEs was 50.8% with the 5 mg dose, 55.9% with the 15 mg dose and 19.4% with placebo, and the incidence of serious TEAEs was 2.3%, 5.6% and 6.3%, respectively.

The incidence of somnolence — which was identified as a TEAE of interest — was similar in the tavapadon groups compared with placebo (3.1% vs. 3.4%). Hallucination, another TEAE of interest, only occurred in the 15 mg group (6.2%). Additionally, the incidence of impulse control disorder was 1% or less in the tavapadon groups.

Pahwa said the safety findings “are supportive of a differentiated mechanism of action with tavapadon compared to current D2/D3 receptor-targeting dopamine agonists.”

“Of course, we will need additional data for that,” he said.

TEMPO-2: Flexible dose

For TEMPO-2, Fernandez and colleagues randomly assigned 304 newly diagnosed, treatment-naive patients to a flexible tavapadon dose ranging from 5 mg to 15 mg daily (n = 151) or placebo (n = 153). Like TEMPO-1, the primary endpoint was the change from baseline in MDS-UPDRS Parts II and III combined.

Also similar to TEMPO-1, the participants’ mean age was about 63 years, and the mean time from diagnosis was less than 1 year.

The mITT population included 150 participants in the tavapadon group and 151 in the placebo group. Eighty participants discontinued the trial.

The primary endpoint was met at week 26, with a 10.3-point reduction in the MDS-UPDRS Parts II and III combined score among participants in the tavapadon group vs. a 1.2 reduction among those in the placebo group.

The majority of TEAEs were mild to moderate in severity. They most often included nausea, headache and dizziness.

The incidence of treatment-related TEAEs was 54.3% in the tavapadon group and 15.7% in the placebo group, and the incidence of serious TEAEs was 4.6% and 1.3%, respectively.

Somnolence was reported in 3.3% of the tavapadon group and 3.9% in the placebo group, and hallucination was only reported in the tavapadon group (4%).

The overall incidence of impulse control disorders was low at 1.3% in the tavapadon group.

“We are very, very encouraged with these results,” Fernandez said.

Researchers are currently investigating the long-term effects of tavapadon in an open-label extension trial.

References:

• Fernandez HH, et al. Efficacy and safety of flexible-dose tavapadon, an oral, once-daily, selective D1/D5 dopamine agonist for the treatment of early Parkinson’s disease. Presented at: American Academy of Neurology Annual Meeting; April 5-9, 2025; San Diego.