Cerevance has initiated dosing in its Phase 3 ARISE trial (NCT06553027) evaluating solengepras as an adjunctive treatment for Parkinson's disease. This global, placebo-controlled study will enroll 330 participants to assess the drug's efficacy over a 12-week period, with topline results anticipated in the first half of 2026.
Solengepras, also known as CVN424, is designed to selectively modulate the GPR6 receptor within the indirect dopamine pathway. Unlike traditional Parkinson's treatments focused on restoring dopamine levels, solengepras aims to target specific brain circuits responsible for motor control and non-motor functions, potentially reducing motor complications like dyskinesia and OFF periods.
The ARISE trial will evaluate two doses of solengepras (75 mg and 150 mg) against a placebo. The primary endpoint is the change in total daily OFF time over the 12-week treatment period. Secondary outcomes include changes in ON time without troublesome dyskinesia, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II scores, patient and clinician global scales, Epworth Sleepiness Scale, and cognitive function as measured by the Cogstate digital cognitive battery.
Inclusion and Exclusion Criteria
Eligible participants must have a diagnosis of Parkinson's disease based on UK Brain Bank and MDS Research Criteria, exhibiting bradykinesia, motor asymmetry, or rest tremor, and a prominent response to levodopa. Additional criteria include a BMI between 18.0 and 35.0 kg/m², a Modified Hoehn and Yahr Stage of at least 3 in the ON state, and the ability to ambulate freely. Cognitive function should be adequate (MoCA ≥ 24), and PD medications must be stable. Exclusion criteria include secondary or atypical parkinsonism, severe dyskinesias or OFF periods that could hinder study participation, prior surgical or therapeutic interventions like deep brain stimulation, clinically significant orthostatic hypotension, hallucinations requiring antipsychotics, and routine use of strong CYP3A4/5 inhibitors or dopamine antagonists.
Prior Phase 2 Results
Prior to the Phase 3 trial, a Phase 2 study published in The Lancet Discovery Science Suite demonstrated solengepras's efficacy and safety. The study met its primary endpoint, showing a statistically significant reduction in average daily OFF time from baseline at day 27 in the 150 mg dose cohort (1.3 hours, P = .02) compared to placebo, representing a 1.6-hour improvement from baseline (P < .0001). Trends towards increased total daily ON time without troublesome dyskinesia were also observed. A supplementary post-hoc analysis showed that higher doses of solengepras reduced OFF time by -1.78 hours (P = .0045) compared to placebo and increased good ON time by +1.3 hours (P = .04). Patients in the solengepras 150 mg group also showed an improved ESS score of -1.35 (±0.68) compared with placebo (P = .049).
Cerevance's Perspective
"Parkinson disease is the fastest growing neurological disorder globally, highlighting a significant need for more improved and effective therapies," said Craig Thompson, chief executive officer at Cerevance. Sagar Vaidya, MD, PhD, chief medical officer at Cerevance, added, "The initiation of ARISE builds on the encouraging Phase 2 data we have generated and represents an exciting chapter in Cerevance’s journey to address the unmet needs of individuals with Parkinson disease."
