Boston, Massachusetts-based Cerevance reported positive topline Phase III results for solengepras (CVN424), with the oral GPR6 inhibitor reducing daily OFF time in people with Parkinson’s disease who continued to experience motor fluctuations despite levodopa and other therapies.
OFF periods occur when the benefit of dopaminergic treatment wears off and symptoms such as slowness, stiffness, tremor, and impaired movement return or worsen. In the randomized, double-blind, placebo-controlled ARISE study, which enrolled 341 patients with an average 5.65 hours of OFF time per day, solengepras 150 mg reduced daily OFF time by an additional 0.61 hours, or about 37 minutes, versus placebo at Week 12 (p=0.0350), meeting the primary endpoint.
The 150 mg dose also increased ON time without troublesome dyskinesia by 0.60 hours versus placebo (p=0.0468) and improved MDS-UPDRS Part II, a measure of activities of daily living, by 1.91 points (p=0.0008). Solengepras was generally well tolerated, with adverse-event discontinuation rates of 3.5% across all groups and no serious adverse events reported with the 150 mg dose.
Solengepras inhibits GPR6, a receptor involved in the indirect basal ganglia pathway, offering a non-dopaminergic approach to motor fluctuations. The Phase III result follows mixed earlier development: a Phase II monotherapy study in early, untreated Parkinson’s disease failed its primary motor endpoint, while a separate adjunctive Phase II study in levodopa-treated patients showed a significant reduction in OFF time.