Cerevance has announced the publication of positive results from its Phase 2 clinical trial of solengepras (CVN424) in eClinicalMedicine, a journal by The Lancet Discovery Science Suite. The trial demonstrated that solengepras, a potentially first-in-class, oral, once-daily, non-dopaminergic, GPR6 inverse agonist, significantly reduced OFF time in individuals with Parkinson’s disease and was generally well-tolerated.
The Phase 2 trial met its key efficacy endpoint by showing a reduction in average daily OFF time from baseline at Day 27, as recorded by patient motor diaries.
Efficacy Results
On Day 27, patients in the solengepras 150 mg group experienced a -1.6 hour change from baseline in daily OFF time (p < 0.0001), while the 50 mg group saw a -1.3 hour change (p < 0.01), and the placebo group a -0.5 hour change. The placebo-adjusted least squares mean treatment difference was statistically significant for the 150 mg dose at -1.3 hours (p=0.0225).
These decreases in OFF time were accompanied by trends towards increased total daily ON time without troublesome dyskinesia. The placebo-adjusted least squares mean treatment difference for good ON time was +0.67 (p=0.27) with the solengepras 150 mg dose.
A supplementary post-hoc analysis, applying a typical regulatory standardized analysis and evaluating patients with ≥3 hours of OFF time at baseline, confirmed the primary analysis findings and showed additional improvement. In this analysis, the solengepras 150 mg group reduced OFF time by -1.78 hours (p=0.0045) compared to placebo and increased good ON time by +1.3 hours (p=0.04).
Favorable trends were also observed for solengepras on key secondary endpoints. At Day 15, participants in the 150 mg group demonstrated a significantly improved ESS score of -1.35 ± 0.68 compared to placebo (p=0.049).
Safety and Tolerability
Solengepras was generally well tolerated, with no serious treatment-related adverse events reported. The most common treatment-emergent adverse events (>5%) were headache and nausea, which were generally mild and transient.
Mechanism of Action
Solengepras is designed to provide a novel approach to Parkinson’s disease treatment. Unlike dopaminergic therapies, solengepras selectively addresses the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, it aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, potentially reducing the risk of dyskinesias and motor fluctuations.
Ongoing Clinical Trials
Solengepras is currently being evaluated as a once-daily, oral treatment in both a monotherapy (Phase 2 ASCEND clinical trial) and as an adjunctive therapy to levodopa and other anti-Parkinsonian medication (Phase 3 ARISE clinical trial).
Parkinson's Disease Context
Parkinson’s disease is a progressive neurodegenerative disorder affecting over ten million people worldwide. Current treatments primarily rely on dopaminergic therapies, which often lose effectiveness over time and are associated with challenging side effects.
