Solengepras reduced average daily OFF time by 1.3 hours versus placebo after 27 days (p=0.02) in a randomized Phase 2 study of Parkinson’s patients with motor fluctuations. In the subgroup with at least three hours of baseline OFF time (88% of participants), a regulatory-aligned analysis showed a 1.78-hour reduction versus placebo (p=0.0045), a 34.7% improvement in total daily OFF time from baseline versus placebo (p=0.0026), nearly one fewer OFF episode per day (−0.98; p=0.0026), and a 26-minute shortening of each OFF period (p=0.0958). The agent was well tolerated with a low incidence of dopaminergic adverse events.
Cerevance presented the data at the 2025 Parkinson Study Group Annual Meeting, where it was selected for the Poster Tour, and confirmed that its pivotal Phase 3 ARISE trial is underway and enrolling. ARISE is a global, 12-week, multicenter study randomizing approximately 330 patients with at least three hours of daily OFF time to once-daily solengepras 75 mg, 150 mg, or placebo on top of levodopa and other background therapies. The primary endpoint is the change from baseline in average daily OFF time at week 12 for the 150 mg dose, with secondary measures spanning ON time, non-motor symptoms, cognition, and quality-of-life instruments. Topline results are targeted for 2026.
Strategically, Cerevance is positioning solengepras as a non-dopaminergic adjunct intended to smooth motor fluctuations without further amplifying dopaminergic signaling. By inhibiting GPR6 and targeting the indirect pathway, the company is seeking efficacy on OFF time with a differentiated safety and tolerability profile versus dopamine-enhancing add-ons. The Phase 2 “normalized regulatory analysis,” which focused on patients with at least 3 hours of baseline OFF, aligns with the inclusion criteria and effect-size expectations common to registrational programs in fluctuating Parkinson’s disease, signaling a conscious effort to de-risk endpoint selection and population definition ahead of Phase 3.
The move has practical implications across the ecosystem. For sites, the ARISE design relies on diary-based OFF quantification over 12 weeks, including morning OFF capture, which will pressure ePRO adherence strategies and may invite supplemental sensor use at high-enrolling centers to control variability. For CROs and vendors, execution hinges on tight data quality controls for patient-reported OFF measures, consistent titration of background regimens, and rigorous morning assessments that often drive the treatment effect. For sponsors and payers, a once-daily, non-invasive adjunct that reduces OFF episodes could offer an operationally simpler alternative to on-demand rescue or device-assisted options, provided the efficacy and safety signals hold over a longer duration. Regulators will be focused on reproducibility of the OFF reduction in a global population, dose-response clarity between 75 mg and 150 mg, and the extent to which non-motor and functional endpoints corroborate the primary signal.
The next inflection point is durability: the Phase 2 readout covered four weeks, while registrational success will require a stable effect through 12 weeks and beyond. Placebo response in PD diaries, site-to-site variability in OFF attribution, and the sensitivity of morning OFF to concomitant therapy adjustments are operational risks that could compress effect size. Watch for enrollment cadence across U.S. and European sites, interim signals on dose separation and safety, and whether the program incorporates long-term extension data that address sustained benefit and tolerability. If ARISE reproduces the magnitude seen in the ≥3-hour baseline OFF population with acceptable safety, solengepras could expand the adjunctive toolkit without adding dopaminergic burden; if not, the path may hinge on biomarker or subgroup strategies to refine who benefits most.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
