Cerevance's drug solengepras helps reduce off-time

Cerevance's experimental oral drug, solengepras (CVN424), was added to standard Parkinson’s disease treatments in a Phase 2 trial and showed promising results. The drug significantly reduced "off time"—periods when symptoms return or worsen, despite treatment. This finding was based on data from a completed clinical trial, which met its main goal of reducing off time, as highlighted in a press release from the company. Cerevance's CEO, Craig Thompson, shared his excitement about the results, stating that solengepras has the potential to become a valuable treatment option for people with Parkinson’s. It aims to help with not only motor symptoms but also improve overall quality of life. The full trial results were published in the medical journal eClinicalMedicine under the title “CVN424, a GPR6 inverse agonist, for Parkinson’s disease and motor fluctuations: a double-blind, randomized, phase 2 trial.” Parkinson’s disease occurs due to the loss of nerve cells in the brain that produce dopamine, a chemical necessary for controlling muscle movement. Levodopa, a common treatment, helps by increasing dopamine levels. However, as the disease advances, patients experience off periods when symptoms like tremors and uncontrolled movements (dyskinesia) come back, even while on medication. These off periods can greatly impact quality of life. Solengepras is a small oral drug designed to enter the brain and work on specific cells that control movement in the striatum, a brain area responsible for voluntary motion. It blocks a protein receptor called GPR6 in these cells, which helps regulate movement. By blocking GPR6, solengepras is expected to provide the same benefits as levodopa but with fewer side effects, particularly dyskinesia. Less Off Time, More On Time with Solengepras The Phase 2 trial enrolled 141 Parkinson’s patients, ages 30 to 80, who had been taking a stable dose of levodopa and other Parkinson’s medications for at least 30 days prior. At the start of the trial, they were experiencing an average of two or more hours of off time each day. The participants were split into three groups: one received a low dose of solengepras (50 mg), another a high dose (150 mg), and the third group received a placebo. The treatment lasted 28 days, and 127 patients completed the full course. Results showed that solengepras led to a dose-dependent reduction in off time. Those on the low dose saw their off time reduced by an average of 1.3 hours compared to the placebo group, while the high-dose group experienced a reduction of 1.6 hours—a statistically significant improvement. This reduction in off time also led to an increase in on time, the period when symptoms were well controlled. In the high-dose group, on time increased by an average of 0.67 hours. Further analysis of patients who initially had over three hours of off time showed even greater benefits. The high-dose group had an average reduction in off time of 1.78 hours compared to the placebo, and their on time increased by 1.3 hours. Other Benefits The trial also revealed that patients taking solengepras experienced less sleepiness, as shown by lower scores on the Epworth Sleepiness Scale (ESS). In the high-dose group, scores dropped by an average of 1.35 points compared to the placebo after 15 days, a significant improvement. Solengepras was generally well tolerated. No serious side effects related to the treatment were reported, with the most common side effects being mild headaches and nausea, which didn’t last long. In addition to this study, solengepras is currently being tested as a standalone treatment in the Phase 2 ASCEND clinical trial and as an add-on to levodopa in a Phase 3 study, both of which are ongoing.