Cerevel Therapeutics’ tavapadon (formerly known as PF-06649751) is a selective partial agonist of the dopamine D1 and D5 receptors, and is given as an oral once-daily tablet. D1 and D5 belong to the same family of dopamine receptors that bind to the neurotransmitter dopamine. When dopamine is present at low levels, like it is in Parkinson’s disease, individuals begin to experience dyskinesia (involuntary body movements).
The trial’s results were presented in a scientific poster, “Efficacy, Safety and Tolerability of Tavapadon in Subjects With Early Stage Parkinson’s Disease,” by David Gray, PhD, Cerevel’s vice president of chemistry and the trial’s team leader, during the 2019 International Congress of Parkinson’s Disease and Movement Disorders, recently held in Nice, France.
The international, double-blind Pfizer-sponsored Phase 2 study (NCT02847650) included 57 patients from 45 to 80 years old. All had early-stage Parkinson’s, as defined by stages 1 to 3 in the Hoehn & Yahr scale of disease severity. After nine weeks to optimize tavapadon’s dose, the treatment period included six more weeks of stable dosing.
The primary efficacy endpoint, or goal, was the change from baseline in the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score of motor function.
At week 15, this score was lower (indicating improvement) with both tavapadon and a placebo, but the reduction was significantly greater with the treatment candidate (9.0 vs. 4.3 points).
Half of the patients treated with tavapadon reported being “much improved” or “very much improved,” compared with 25% in the placebo group, when assessed with the Patient Global Impression of Change (PGI-C). In contrast, no benefits were seen in daytime sleepiness in weeks 9 and 15, as measured with the Epworth Sleepiness Scale.
Tavapadon was found to be safe and well-tolerated, with most adverse events being mild or moderate. In the group taking this experimental therapy, the most common side effects were nausea, headache, sleepiness, dry mouth, and tremors.
Treatment adherence was high in both groups, with 82% of the patients on tavapadon completing the trial.
“I’m encouraged by these results, which demonstrated that tavapadon was significantly more effective than placebo in improving motor symptoms and was well-tolerated,” Gray said in a news release. “It has the potential to be a promising new treatment option for people with Parkinson’s.”
Although a previous study of tavapadon (NCT02687542) was terminated early due to lack of efficacy in moderate to advanced Parkinson’s, the “favorable profile of tavapadon in clinical studies to date” support its potential “both as a monotherapy for patients with early-stage disease and as an adjunct to levodopa for patients with late-stage disease,” said Raymond Sanchez, MD, chief medical officer at Cerevel (which was launched by Pfizer and Bain Capital in October 2018).
The company plans to start a Phase 3 trial in 2020 to investigate tavapadon in patients with early- and late-stage Parkinson’s.