At the American Academy of Neurology (AAN) 2026 annual conference, Cerevance reported findings from the Phase II ASCEND (NCT06006247) trial evaluating solengepras, a novel GPR6 inhibitor, in patients with early, untreated Parkinson’s disease (PD). The study emphasises the increasing focus on non-motor symptoms in PD, particularly sleep disturbances, which remain inadequately addressed by current dopaminergic therapies. As highlighted by key opinion leaders (KOLs) previously interviewed by GlobalData, symptoms such as sleep dysfunction, fatigue, and cognitive impairment represent significant unmet needs in PD management.
Solengepras is an oral, brain-penetrant, highly selective GPR6 inhibitor that modulates inhibitory signalling in the indirect basal ganglia pathway, indirectly influencing dopaminergic tone without directly targeting dopamine receptors. The ASCEND study was a randomised, placebo-controlled trial in early PD patients receiving solengepras 150mg or placebo once daily over 12 weeks. The primary endpoint assessed change in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III, with secondary endpoints evaluating non-motor symptoms, including sleep.
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While the primary motor endpoint showed modest improvement (-0.73 versus placebo), more notable effects were observed in non-motor domains. Solengepras improved MDS-UPDRS Part I scores (-1.01 at Week 12), with consistent benefits seen in sleep-related measures, including MDS-UPDRS sleep components and Epworth Sleepiness Scale (ESS) scores. These findings support the therapeutic potential of targeting non-dopaminergic pathways to address symptoms that are poorly managed by standard treatments.
Component-improvements were observed favouring solengepras in sleep, autonomic symptoms, and behaviour, with a minimal impact on cognition and mood. This profile aligns with the mechanism of GPR6 inhibition, which involves the modulation of basal ganglia circuitry without the overstimulation of dopaminergic pathways.
Solengepras was well tolerated, with no serious adverse events or discontinuations reported. Adverse events were comparable to placebo and included dizziness, headache, insomnia, and orthostatic hypotension. This favourable safety profile is particularly important in early PD populations that require long-term treatment.
The PD market is dominated by dopaminergic therapies, levodopa combinations, dopamine agonists, and monoamine oxidase-B (MAO-B) inhibitors, none of which adequately address non-motor symptoms. KOLs previously interviewed by GlobalData consistently identified sleep dysfunction, fatigue, and cognitive impairment as being among the most debilitating and poorly managed aspects of PD, with several KOLs noting that patients frequently prioritised non-motor symptom relief over incremental motor gains. Solengepras would enter a non-motor space with no approved disease-specific treatments, which represents a genuine first-mover opportunity if the Phase III data replicate the ASCEND signal.
However, the modest and statistically non-significant motor benefit and the relatively small sample size of 64 participants mean that the ASCEND data should be interpreted cautiously. The potential open-label extension and further pivotal studies will be critical in determining whether the non-motor benefits are durable. If sustained, solengepras’s differentiated mechanism and favourable tolerability could support its positioning, and it may serve as an early intervention therapy targeting non-motor symptoms, potentially alongside dopaminergic treatments. Overall, the ASCEND trial highlights the importance of expanding PD treatment strategies beyond motor symptom control and supports GPR6 inhibition as a novel therapeutic approach.
