New Parkinson’s drug reduces OFF time without targeting dopamine

As Parkinson’s disease progresses, patients may experience periods when medication benefit wanes and motor symptoms return. Treating these “OFF” periods while limiting dyskinesia and other adverse effects remains challenging.

Investigational solengepras reduced daily OFF time in the phase 3 ARISE trial, according to Cerevance’s topline results presented at the International Congress of Parkinson’s Disease and Movement Disorders. The once-daily oral drug inhibits GPR6, a receptor involved in brain circuits controlling movement, without directly targeting dopamine receptors.

ARISE randomized 341 adults with motor fluctuations to solengepras 75 mg, 150 mg, or placebo for 12 weeks while continuing their usual Parkinson’s medications. Participants averaged 5.65 hours of daily OFF time at baseline.

At week 12, the 150 mg dose reduced daily OFF time by 1.56 hours versus 0.95 hours with placebo—an additional 0.61 hours, or approximately 37 minutes. Separation from placebo appeared by week two. ON time without troublesome dyskinesia increased by approximately 36 additional minutes daily versus placebo.

Everyday motor function also improved. Smaller improvements in daytime sleepiness and exploratory quality-of-life measures suggest possible benefits beyond motor fluctuations, although those findings are less definitive.

Most adverse events were mild or moderate. Adverse event discontinuation was 3.5% in each group. Dyskinesia occurred in 4.4% with 150 mg versus 1.8% with placebo. Headache, urinary tract infection, insomnia, and nausea were the most frequently reported adverse events.

“Daily function, alertness, and quality of life are measures that reflect how people with Parkinson's experience their day,” said Craig Thompson, chief executive officer of Cerevance. The company plans to meet with the FDA to discuss the results and next steps toward a potential New Drug Application.

Source: Cerevance. (2026 Oct 7) Cerevance announces positive phase 3 ARISE results: Once-daily oral solengepras meets primary endpoint and demonstrates motor and non-motor benefits in Parkinson’s disease