Phase 2 data from the ASCEND trial of solengepras signaled potential benefit on functional and non-motor measures in early Parkinson’s disease over 12 weeks, with the agent generally well tolerated and a low rate of dopaminergic side effects reported.
Cerevance will present the ASCEND findings in an oral session at the 2025 MDS International Congress on October 6. Solengepras (CVN424) is a once-daily, oral GPR6 inhibitor designed to modulate the indirect pathway without directly affecting dopamine signaling. While ASCEND was a mid-stage study, the program has already advanced into the Phase 3 ARISE trial, positioning solengepras as an adjunct to levodopa and other anti-Parkinsonian therapies. The company indicates that the analysis to be presented will cover functional and non-motor outcomes alongside safety observations.
The strategy is clear: establish a non-dopaminergic symptomatic option that can complement levodopa while avoiding dyskinesias and motor fluctuations often tied to dopaminergic add-ons. Targeting GPR6 reflects a selective, circuit-level approach aimed at addressing both motor and non-motor burden—an area where traditional dopaminergic strategies have had uneven impact and where regulatory and payer interest has grown. Presenting positive signals ahead of a pivotal readout builds clinical mindshare and sets expectations around endpoints that extend beyond MDS-UPDRS Part III. The tension is the usual one for Parkinson’s symptomatic agents: short-duration, mid-stage signals in functional and non-motor domains must translate into durable, clinically meaningful effects in a larger, heterogeneous population where placebo response is nontrivial.
For sites, a non-dopaminergic adjunct in early PD could be operationally straightforward—background levodopa use broadens eligibility and reduces washout complexity—while a low incidence of dopaminergic adverse events may ease monitoring. However, if the pivotal relies on non-motor and functional measures, expect heavier reliance on rater-dependent scales and patient-reported outcomes, with the associated training and inter-rater variability risks. CROs and vendors should anticipate emphasis on standardized rater certification, centralized review, and robust ePRO capture to control noise. Sponsors watching the space will note whether Cerevance leans into composite endpoints that reflect daily function, which aligns with ongoing regulatory attention to outcomes patients value, but can complicate powering and analysis plans. Regulators and payers will look for consistency across subgroups and domains, and for evidence that benefits translate to real-world function without new safety trade-offs.
What matters next are the details missing from the topline: effect size on pre-specified endpoints, variability, responder analyses, and domain-level performance within non-motor measures. Durability beyond 12 weeks remains an open question, as do interactions with standard regimens over longer exposure. Clarity on ARISE’s primary endpoint selection, statistical hierarchy across motor and non-motor readouts, and the scale of the safety database will signal regulatory confidence. If the Phase 3 design adequately addresses placebo mitigation, rater consistency, and early PD heterogeneity, solengepras could emerge as a differentiated adjunct in a market crowded with dopaminergic boosters but few non-dopaminergic options with broad functional impact. The risk is familiar: past non-dopaminergic approaches have stumbled between mid-stage promise and pivotal robustness. Watch for whether the Congress presentation discloses sufficient quantitative granularity to justify the pivotal bet and for any indication of digital or longitudinal outcome measures that could tighten signal detection in Phase 3.
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.
