Solengepras Meets Primary Endpoint in Phase 3 ARISE Trial of Parkinson Disease

In the movement disorder realm, the phase 3 ARISE trial met its primary endpoint, with once-daily oral solengepras (Cerevance) 150 mg significantly reducing OFF time compared with placebo in patients with Parkinson disease (PD) who experience motor fluctuations. Cerevance, which develops solengepras, presented the results at the 2026 International Congress of Parkinson's Disease and Movement Disorders (MDS Congress) in Seoul, South Korea.¹

“[Solengepras] met its primary endpoint and showed a consistent pattern of benefit,” said Craig Thompson, chief executive officer of Cerevance, said in a statement. The company said it looks forward to discussing the results with the FDA to determine next steps.²

ARISE (NCT06553027) was a randomized, double-blind, placebo-controlled, international trial in patients with PD with motor fluctuations on stable background PD medications, who averaged at least 3 hours of total daily OFF time (at least 2.5 hours each day) by home diary. Of 710 participants screened, 341 were randomized 1:1:1 to solengepras 150 mg (n = 113), 75 mg (n = 114), or matching placebo (n = 114) once daily for 12 weeks, across sites in the United States, European Union, United Kingdom, and Australia. Baseline average daily OFF time was 5.65 hours.^1,2

The primary endpoint was change from baseline to week 12 in average daily OFF time. Secondary endpoints included change in ON time without troublesome dyskinesia, MDS-UPDRS Part II and III scores, and the Epworth Sleepiness Scale (ESS). Overall, treatment with solengepras 150 mg reduced average daily OFF time by 1.56 hours from baseline, compared with 0.95 hours with placebo, a between-group difference of 0.61 hours (P =.035); the benefit was apparent as early as week 2 (0.75-hour difference; nominal P =.0022).²

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On key secondary endpoints, the 150 mg group showed a 1.58-hour increase in ON time without troublesome dyskinesia from baseline, compared with 0.98 hours with placebo (difference, 0.60 hours; P =.0468), and a 2.05-point improvement on MDS-UPDRS Part II, compared with 0.14 points with placebo (difference, 1.91 points; P =.0008). The Epworth Sleepiness Scale improved by 1.39 points, compared with 0.41 points with placebo (difference, 0.98 points; nominal P =.009), and the exploratory PDQ-39 quality-of-life measure improved by 3.73 points, compared with 0.86 points with placebo (difference, 2.87 points; nominal P =.012).²

“Looking at these measures together may give a fuller picture of a treatment's potential benefits” for patients experiencing motor fluctuations, study author Robert A. Hauser, MD, MBA, director of the Parkinson's Disease and Movement Disorder Center at the University of South Florida.²

Of 341 randomized participants, 91% (311) completed the 12-week trial. Discontinuation due to adverse events (AEs) occurred in 3.5% of participants across all 3 arms, including placebo. No serious AEs occurred in the 150 mg group. The most common AEs with 150 mg, versus placebo, were headache (8.0% vs 3.5%), urinary tract infection (8.0% vs 6.1%), insomnia (6.2% vs 0.9%), and nausea (6.2% vs 1.8%); dyskinesia occurred in 4.4% of the 150 mg group versus 1.8% with placebo.²

Mechanism and earlier phase 2 data

Solengepras (CVN424) is a brain-penetrant, specific inhibitor of GPR6, a receptor found primarily on medium spiny neurons of the indirect pathway that regulates movement. Unlike dopaminergic therapies, it is designed to help restore balance between the direct and indirect basal ganglia pathways without directly altering dopamine levels.^1,2

In an earlier 27-day phase 2 trial, treatment with solengepras 150 mg reduced average daily OFF time by 1.3 hours versus placebo (P =.02); among the 88% of participants with at least 3 hours of baseline OFF time, the reduction was 1.78 hours by day 27 (P =.0045), with a 34.7% improvement in total daily OFF time from baseline versus placebo (P =.0026). Solengepras was reported as well tolerated, with a low incidence of dopaminergic AEs.³

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REFERENCES
1. Hauser R, Sarva H, Karbowniczek A, Carroll C, Rascol O, Tisch S, Brice N, Kieburtz K, Ellenbogen A. Results from ARISE: a pivotal phase 3 trial of solengepras in Parkinson's disease with motor fluctuations. Presented at: 2026 International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Late-Breaking Abstract LBA21.
2. 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. News release. Published October 7, 2026. Accessed October 7, 2026. https://www.cerevance.com/media/cerevance-announces-positive-phase-3-arise-results-once-daily-oral-solengepras-meets-primary-endpoint-and-demonstrates-motor-and-non-motor-benefits-in-parkinsons-disease
3. Cerevance showcases positive phase 2 results demonstrating significant reduction in OFF time with solengepras as an adjunctive treatment in Parkinson's disease. News release. Published December 5, 2025. Accessed October 7, 2026. https://www.globenewswire.com/news-release/2025/12/06/3201025/0/en/Cerevance-Showcases-Positive-Phase-2-Results-Demonstrating-Significant-Reduction-in-OFF-Time-with-Solengepras-as-an-Adjunctive-Treatment-in-Parkinson-s-Disease.html