Cerevance’s solengepras met the Phase 3 ARISE primary endpoint, reducing daily OFF time and improving motor function in Parkinson’s disease.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Cerevance’s investigational once-daily oral solengepras met the primary endpoint of the Phase 3 ARISE trial in people with Parkinson’s disease experiencing motor fluctuations despite background treatment. The 150 mg dose significantly reduced daily OFF time compared with placebo and improved ON time without troublesome dyskinesia and motor experiences of daily living. Additional improvements were reported in daytime sleepiness and exploratory quality-of-life measures, while solengepras was generally well tolerated. The company reported these findings as positive topline results from the Phase 3 study.
Solengepras Reduces Daily OFF Time in Phase 3 ARISE
Cerevance evaluated solengepras as an adjunctive therapy for people with Parkinson’s disease experiencing motor fluctuations despite treatment with levodopa and other Parkinson’s disease medications.
The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 ARISE trial enrolled 341 participants and randomized them 1:1:1 to once-daily solengepras 75 mg (n=114), solengepras 150 mg (n=113), or placebo (n=114) for 12 weeks. Participants continued their usual background Parkinson’s disease medications throughout the study. Of the 341 randomized participants, 311 (91%) completed the trial.
At baseline, participants had an average of 5.65 hours of daily OFF time despite their existing treatment.
The primary endpoint assessed the change from baseline to Week 12 in average daily OFF time with solengepras 150 mg compared with placebo.
At Week 12, solengepras 150 mg reduced daily OFF time by 0.61 hours versus placebo (p=0.0350). OFF time decreased by 1.56 hours from baseline with solengepras 150 mg compared with 0.95 hours with placebo.
The reduction was observed as early as Week 2, the first post-baseline assessment. At that time, solengepras 150 mg reduced OFF time by 0.75 hours versus placebo (nominal p=0.0022), with the numerical benefit maintained at subsequent assessments through Week 12.
Improvement in ON Time Without Troublesome Dyskinesia
Solengepras 150 mg also improved the key secondary endpoint of ON time without troublesome dyskinesia.
At Week 12, ON time without troublesome dyskinesia increased by 0.60 hours versus placebo (p=0.0468). The increase from baseline was 1.58 hours with solengepras 150 mg compared with 0.98 hours with placebo.
The finding complements the reduction in daily OFF time observed with solengepras 150 mg and indicates an increase in time spent in an ON state without troublesome dyskinesia.
Motor Experiences of Daily Living Improve
Beyond changes in daily OFF time, solengepras 150 mg improved motor experiences of daily living, measured using MDS-UPDRS Part II as a pre-specified secondary endpoint.
The placebo-adjusted improvement was 1.91 points (p=0.0008). Scores improved by 2.05 points from baseline with solengepras 150 mg compared with 0.14 points with placebo.
The result provides evidence of an improvement in motor experiences of daily living alongside the observed changes in daily ON and OFF time.
Non-motor and Quality-of-Life Measures Show Additional Improvements
Cerevance also reported improvements across selected non-motor measures.
On the Epworth Sleepiness Scale, daytime sleepiness improved by 0.98 points versus placebo (nominal p=0.009). The improvement from baseline was 1.39 points with solengepras 150 mg compared with 0.41 points with placebo.
Quality of life was assessed using the Parkinson’s Disease Questionnaire-39 (PDQ-39) as an exploratory measure. Solengepras 150 mg improved PDQ-39 scores by 2.87 points versus placebo (nominal p=0.012), with a 3.73-point improvement from baseline compared with 0.86 points with placebo.
Because these analyses included nominal p-values and the PDQ-39 assessment was exploratory, the findings should be considered supportive and require further evaluation.
Solengepras Shows Favorable Tolerability
Solengepras was generally well tolerated in ARISE, with most adverse events described as mild or moderate.
Treatment discontinuation because of an adverse event was 3.5% across all three groups, including placebo. No serious adverse events were reported in participants receiving solengepras 150 mg, compared with 1.8% with the 75 mg dose and 0.9% with placebo.
Dyskinesia occurred in 4.4% of participants receiving solengepras 150 mg compared with 1.8% with placebo.
The most frequently reported adverse events with solengepras 150 mg were headache (8.0% vs 3.5% with placebo) and urinary tract infection (8.0% vs 6.1%), followed by insomnia (6.2% vs 0.9%) and nausea (6.2% vs 1.8%).
Cerevance noted that the relatively limited occurrence of typical dopaminergic adverse events may be consistent with solengepras’ non-dopaminergic mechanism.
A Potential Non-dopaminergic Approach to Parkinson’s Disease
Solengepras, also known as CVN424, is designed to selectively inhibit the GPR6 receptor in the striatal indirect pathway.
Unlike conventional dopaminergic therapies, solengepras does not directly act on dopamine receptors. Cerevance is developing the therapy as a non-dopaminergic approach intended to modulate activity within the basal ganglia circuitry involved in Parkinson’s disease motor function.
This mechanism could provide a different therapeutic approach for patients who continue to experience motor fluctuations despite established Parkinson’s disease treatments.
However, solengepras remains investigational and has not been approved for the treatment of Parkinson’s disease.
Next Steps for Solengepras
The ARISE results provide Cerevance with clinical data to support discussions with the U.S. Food and Drug Administration regarding the development program.
The company plans to meet with the FDA to discuss the potential regulatory path toward a New Drug Application (NDA). No NDA submission has been reported at this stage.
The ARISE findings were presented by Robert A. Hauser, M.D., M.B.A., and Karl Kieburtz, M.D., M.P.H., during the 2026 International Congress of Parkinson’s Disease and Movement Disorders in Seoul, South Korea.
With the Phase 3 trial meeting its primary endpoint and demonstrating improvements across selected motor and non-motor measures, upcoming regulatory discussions will help determine the next steps for solengepras as a potential non-dopaminergic treatment option for Parkinson’s disease.
Reference
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 Cerevance, October 7, 2026
To Evaluate the Efficacy of CVN424 in Parkinson’s Disease Participants with Motor Complications, ClinicalTrials.gov ID NCT06553027
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.