Tavapadon (PF-06649751; Cerevel Therapeutics, Boston, MA) has been shown in phase 2 trials to reduce improve motor symptoms of Parkinson disease (PD) as measured with the in Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Tavapadon is a D1 and D5 dopamine receptor partial agonist taken orally once daily. Currently available drugs for better motor control, in contrast, work at the D2 and D3 dopamine receptors.
The first participants have been dosed in all 3 clinical trials in a phase 3 program evaluating tavapadon. Approximately 1,200 individuals age 40 to 80 will be enrolled across all 3 trials. The primary endpoint of the TEMPO-1 (NCT04201093) and TEMPO-2 (NCT04223193) trials is the change from baseline in the MDS-UPDRS part 2 and part 3 combined score. The TEMPO-3 (NCT04542499) trial will measure change from baseline in total daily “ON” time without troublesome dyskinesia. A fourth 58-week, open-label, safety extension trial will also be conducted as part of the program.
“We are encouraged by the benefit-risk profile of tavapadon based on the efficacy results observed in phase 2 trials, as well as the tolerability profile we have seen in our clinical program to date,” said Raymond Sanchez, MD, chief medical officer of Cerevel Therapeutics. “We look forward to advancing the development of tavapadon and potentially bringing a differentiated, cornerstone therapy to individuals with PD at all stages of the disease as supported by a robust phase 3 program.”
Tavapadon has been evaluated in 272 participants in phase 1 and phase 2 trials, including in both early- and late-stage PD populations, as required for a broad indication in PD. Across phase 1b and phase 2 trials conducted to date, tavapadon has demonstrated motor control benefit with the potential for an improved tolerability profile relative to D2/D3-preferring agonists.
The phase 3 program includes 3 27-week double-blind randomized placebo-controlled parallel-group trials designed to evaluate the efficacy, safety, and tolerability of fixed doses (TEMPO-1) and flexible doses (TEMPO-2) of tavapadon as a monotherapy in individuals with early-stage PD or as an adjunctive therapy to levodopa in participants with late-stage PD who are experiencing motor fluctuations (TEMPO-3).
Carlos E.V. Sollero, MD; Hsin-Pin Lin, MD; Miguel Chuquilin, MD; James Wymer, MD; and Aaron M. Carlson, MD
Ganesh M. Babulal, PhD, OTD, and Catherine M. Roe, PhD
Cyrus A. Raji, MD, PhD; Somayeh Meysami, MD; and Mario F. Mendez, MD, PhD