Cerevel’s Tavapadon Meets Primary End Point in Phase 3 TEMPO-3 Study of Parkinson Disease
Tavapadon's phase 3 success complements ongoing monotherapy trials, addressing the need for effective and well-tolerated PD therapies.
Raymond Sanchez, MD
According to a recent announcement, Cerevel Therapeutics’ investigational agent tavapadon, a selective D1/D5 receptor partial agonist in development for Parkinson disease (PD), met its primary end point of change in ON time without troublesome dyskinesia in the phase 3 TEMPO-3 trial (NCT04542499). Full results are expected to be submitted for presentation at future medical meetings and used to support regulatory submissions of tavapadon as a treatment for PD.1
All told, when used as adjunctive to levodopa, patients on tavapadon experienced a clinically meaningful and statistically significant increase of 1.1 hours of total ON time without troublesome dyskinesia compared with those treated with levodopa and placebo (1.7 h vs 0.6 h; P <.0001). Although data was not provided, the company noted that the therapy demonstrated a statistically significant reduction in OFF time, the key secondary end point, in the tavapadon arm.
TEMPO-3, a double-blind, placebo-controlled, parallel-group, flexible-dose, 27-week trial, included 507 adults with PD between the ages of 40-80 years old. In the study, patients were provided with a home diary (Hauser diary) to assess their motor function state. Those included in the study entered experiencing motor fluctuations and were on a stable dose of levodopa for at least 4 weeks prior to screening. Patients were randomly assigned to either tavapadon adjunctive to levodopa, titrated to 5-15 mg, or placebo and levodopa, orally and once-daily.
"Tavapadon’s novel mechanism of action, which selectively activates the D1/D5 dopamine receptors, has demonstrated the potential to provide people living with Parkinson’s disease the right balance of motor control, safety and tolerability," Raymond Sanchez, MD, chief medical officer, Cerevel Therapeutics, said in a statement.1 "We are highly encouraged with the results announced today, and look forward to sharing additional data later this year from the monotherapy trials, TEMPO-1 and TEMPO-2, as we seek to evaluate tavapadon’s potential benefit to people living with Parkinson’s disease."
In the study, tavapadon demonstrated a safety profile that was consistent with previous studies, with a majority of the adverse events (AEs) being mild to moderate in severity. Prior to TEMPO-3, a phase 2, randomized, flexible-dose study revealed AEs of nausea, headache, somnolence, and tremor. The study, comprised of 57 patients aged 45 to 80 years with PD, included a 9-week dose optimization period followed by a 6-week period of stable dosing.
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Announced in 2019, results from the phase 2 study showed that tavapadon met its primary end point of motor symptom improvement after 15 weeks. All told, researchers observed a change of –9.0 points on UPDRS Part 3 scores for those treated with the agent vs changes of –4.3 for those administered placebo (least-square mean, –4.8; P = .0407). Additionally, the treatment compliance was high in both groups, and 82% of patients who received tavapadon completed the trial.
TEMPO-3 is part of a larger phase 3 program that includes TEMPO-1 (NCT04201093) and TEMPO-2 (NCT04223193). TEMPO-1 and TEMPO-2, which assesses tavapadon as a monotherapy, is expected to have topline data read out in the second half of 2024. TEMPO-1 is a fixed-dose trial while TEMPO-2 and TEMPO-3 are flexible dosing. All 3 trials are supported by a 58-week open-label extension that will continue to gather information on safety that will be needed for an eventual FDA submission.
"Parkinson disease is the fastest growing neurodegenerative disorder in the world, and a significant need exists for a new treatment option that provides the right balance of dopamine signaling and delivers sustained motor control without the burdensome side effects associated with current treatments,” principal investigator Hubert Fernandez, MD, James and Constance Brown endowed chair in movement disorders, professor of neurology and director at the Center for Neurological Restoration at Cleveland Clinic, said in a statement.1 "The results from the TEMPO-3 trial are particularly exciting as they demonstrate that tavapadon has the potential to offer an important new option for individuals living with this chronic, debilitating disease."
