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Early Parkinson's Drug Hits Targets in Phase III Studies
Both fixed and flexible doses of investigational tavapadon met primary endpoints
SAN DIEGO -- Both fixed and flexible doses of investigational tavapadon met their primary endpoint in phase III trials of early Parkinson's disease.
In the TEMPO-1 (fixed dose) and TEMPO-2 (flexible dose) studies, participants receiving tavapadon as monotherapy had a significant reduction in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II and III combined scores at week 26 compared with placebo, researchers said in two late-breaking presentations at the American Academy of Neurology annual meeting.
Part II of the MDS-UPDRS measures activities of daily living. Part III assesses motor symptoms including tremors, rigidity, bradykinesia, and postural instability. Combined scores for parts II and III range from 0-184 points (0-52 for part II and 0-132 for part III), with higher scores indicating more severe impairment.
In TEMPO-1, two fixed doses of tavapadon -- 5 mg and 15 mg -- showed lower combined part II and III scores versus placebo, said Rajesh Pahwa, MD, of the University of Kansas Medical Center in Kansas City. Compared with placebo, combined scores were better by a mean difference of -11.5 points (95% CI -13.8 to -9.2, P<0.0001) for the 5-mg dose and -12.1 points (95% CI -14.4 to -9.8, P<0.0001) for the 15-mg dose.
In TEMPO-2, the mean difference in combined part II and III scores versus placebo was -9.1 points (95% CI -11.7 to -6.5, P<0.0001) with flexible doses of tavapadon, reported Hubert Fernandez, MD, of the Cleveland Clinic.
Tavapadon is an oral selective D1/D5 dopamine agonist that's being investigated as both monotherapy and adjunctive therapy to levodopa in Parkinson's disease. "A key unmet need in Parkinson's disease is finding a treatment modality that can balance the good effects of dopamine stimulation while reducing the side effects, especially idiosyncratic side effects, known in D2 and D3 agonism," Fernandez said.
Both studies were double-blind trials evaluating tavapadon as monotherapy for adults with early Parkinson's disease. Participants were at Hoehn and Yahr stage 1-2 and had been diagnosed less than 3 years ago.
Change from baseline in the combined MDS-UPDRS part II and III scores at week 26 was the primary endpoint. Change in MDS-UPDRS part II scores was a key secondary endpoint.
TEMPO-1 randomized 529 participants 1:1:1 to receive 5 mg or 15 mg of tavapadon once daily or placebo. Mean age was 63.7 years, 64.7% were male, and mean duration since Parkinson's diagnosis was 0.73 years. Mean combined part II and III scores were 31.8 points at baseline. Overall, 129 participants discontinued the trial.
TEMPO-2 included 304 adults randomized 1:1 to receive flexible-dose tavapadon or placebo. Tavapadon doses were 5 to 15 mg once daily, titrated to the maximum tolerated dose. Mean age was 62.9 years, 55.6% were male, and mean duration since Parkinson's diagnosis was 0.86 years. Mean part II and III scores combined were 30.5 points at baseline. A total of 80 participants discontinued the trial.
Both studies met the secondary outcome of change in MDS-UPDRS part II scores. In TEMPO-1, tavapadon had better part II scores versus placebo at both the 5-mg dose (mean difference -2.5 points, P<0.0001) and the 15-mg dose (mean difference -2.6 points, P<0.0001). In TEMPO-2, the part II score was better with flexibly dosed tavapadon compared with placebo (mean difference -1.5 points, P=0.0007).
Safety data appeared to be consistent with prior tavapadon trials. In both studies, nausea, headache, and dizziness were the most common treatment-emergent adverse events and the most common events leading to treatment discontinuation.
"The incidence of somnolence and other D2/D3 receptor idiosyncratic reactions were indistinguishable from placebo," Fernandez noted. "These are short-term studies and require long-term confirmation," he added.
In the TEMPO-1 study, 6.2% of the 15-mg group experienced hallucinations. One death occurred in the 5-mg group; the cause was unknown. In the TEMPO-2 study, 4% who received tavapadon experienced hallucinations and there were no deaths.
A trial assessing tavapadon as adjunctive therapy (TEMPO-3) has also been completed. An open-label extension study evaluating the long-term use of the drug (TEMPO-4) is ongoing.
Disclosures
The TEMPO trials were supported by AbbVie.
Pahwa disclosed compensation for consultancy and research funding from AbbVie.
Fernandez reported serving as a consultant and as an advisory board member for AbbVie.
Primary Source
American Academy of Neurology
Source Reference: Pahwa R "Efficacy and safety of fixed-dose tavapadon, an oral, once-daily, selective D1/D5 dopamine agonist for the treatment of early Parkinson's disease" AAN 2025.
Secondary Source
American Academy of Neurology
Source Reference: Fernandez HH "Efficacy and safety of flexible-dose tavapadon, an oral, once-daily, selective D1/D5 dopamine agonist for the treatment of early Parkinson's disease" AAN 2025.
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