Tavapadon’s flexible dose eases symptoms in early Parkinson’s
Top-line data from Phase 3 trial show significant motor symptom lessening
A flexible dose of experimental oral treatment tavapadon significantly lessened motor symptoms in adults with early-stage Parkinson’s disease, according to top-line results from a completed Phase 3 clinical trial.
Developer Abbvie expects to present full results of the study, TEMPO-2 (NCT04223193), at a future medical meeting and to use them to support regulatory submissions seeking the therapy’s approval. The company said it’s “on track” to submit a new drug application to the U.S. Food and Drug Administration (FDA) in 2025.
Tavapadon was tested as a single fixed-dose therapy in early-stage Parkinson’s patients in the Phase 3 TEMPO-1 trial (NCT04201093) and as an add-on to standard levodopa in late-stage Parkinson’s patients in the Phase 3 TEMPO-3 study (NCT04542499).
“The results from TEMPO-2, and across the entire TEMPO clinical development program, add to the growing evidence which suggests that tavapadon has the potential to offer an important new option for individuals living with Parkinson’s disease,” Hubert H. Fernandez, MD, global principal investigator of the program and director of the Center for Neurological Restoration at Cleveland Clinic, said in an Abbvie press release.
In Parkinson’s, the progressive loss of nerve cells that produce dopamine, a chemical messenger important for motor control, leads to the disease symptoms, including tremors, rigidity, slowness of movement, and walking and balance issues.
Early Parkinson’s patients see results
“Parkinson’s disease imposes a profound burden on individuals living with this challenging neurological condition, significantly affecting their quality of life and management of daily activities,” Fernandez said. “Right now, there is still an unmet need for treatments that deliver efficacy while minimizing unwanted side effects.”
Tavapadon is an orally available molecule that mimics the action of dopamine by partially activating D1 and D5 dopamine receptors at the surface of neurons. This is expected to help ease motor symptoms.
In the placebo controlled TEMPO-1 study, early-stage Parkinson’s patients taking tavapadon as a once-daily, fixed-dose single therapy were shown to experience significantly greater motor function improvements relative to those given a placebo.
TEMPO-3 data showed that a flexible dose of tavapadon (5 to 15 mg daily), given once a day as an add-on to levodopa, significantly increased on time without troublesome dyskinesia in advanced Parkinson’s patients, compared with a placebo.
On time refers to periods when medication effectively controls motor symptoms, and dyskinesia refers to sudden, involuntary movements that are commonly associated with levodopa’s long-term use.
Positive results in 3 trials
The TEMPO-2 study evaluated the efficacy, safety, and tolerability of tavapadon, as a flexible-dose single therapy, against a placebo in 304 adults, ages 40 to 80, with early Parkinson’s.
Participants, who were living with the disease for less than three years, were randomly assigned to receive either tavapadon, at a dose between 5 mg and 15 mg, or a placebo, once daily for 27 weeks (about six months).
The study’s main goal was to assess changes in motor symptom severity using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts 2 and 3 combined score. Higher scores indicate more severe symptoms and disability.
Newly announced results showed that tavapadon treatment resulted in a significantly greater score reduction relative to a placebo (10.3 points vs. 1.2 points). Tavapadon was also associated with significantly greater, and clinically meaningful, improvements in motor aspects of daily living experiences, as assessed by MDS-UPDRS-Part 2, meeting the trial’s key secondary goal.
The therapy’s safety profile was consistent with that reported in previous trials, with most adverse events being mild to moderate in severity.
“The positive results across all three Phase 3 TEMPO trials underscore the potential of tavapadon as a first-in-class D1/D5 partial [activator] for the treatment of Parkinson’s disease,” said Primal Kaur, MD, AbbVie’s senior vice president of immunology, neuroscience, eye care, and specialty development. “With these data in hand, we look forward to working with regulatory agencies to assess next steps, bringing us one step closer to providing tavapadon for those living with this chronic, debilitating disease.”
Patients completing any of the three placebo-controlled Phase 3 trials of tavapadon may choose to enroll in the Phase 3 TEMPO-4 study (NCT04760769), where all will receive flexible doses of tavapadon for about one year to assess its long-term safety and efficacy.
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