At the recently held AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Disease (PD), Cerevance announced that solengepras, a first-in-class G-protein coupled receptor 6 (GPR6) antagonist in development for early PD, failed to meet its primary endpoint in the Phase II ASCEND trial as a monotherapy. Despite the failure solengepras has shown promise in other clinical trials as an adjunctive therapy, indicating that it is more likely to be positioned as an adjunctive therapy if it reaches market, says GlobalData, a leading data and analytics company.

Jos Opdenakker, Neurology Analyst at GlobalData, comments: “Solengepras failed to meet its primary endpoint, as patients treated with the drug experienced a small, non-statistically significant improvement from baseline compared to placebo in the MDS-UPDRS Parts II and III combined score at week 12. According to Cerevance, the results missed the statistical bar primarily because of the lack of differentiation between solengepras and placebo in the Part III physician-administered neurological exam.”

Despite missing the primary endpoint, Cerevance said the trial saw trends in improvement on other patient-reported measures. These included benefits in non-motor symptoms, daily function, overall non-motor symptom burden, and daytime sleepiness.

Furthermore, Solengepras was well-tolerated as a monotherapy, with all subjects completing the 12-week trial period and no serious adverse events (AEs) being reported. In the ASCEND trial, only 25% of the participants who received solengepras experienced any treatment emergent adverse events (TEAEs). This indicates that solengepras does have a role to play in the PD treatment landscape.

Opdenakker explains: “Solengepras has shown promise as an adjunctive therapy, achieving a clinically meaningful reduction in OFF time with minimal dopaminergic side effects in a Phase II trial in PD patients with motor fluctuations.”

Moreover, Cerevance is moving forward with its pivotal Phase III ARISE trial, which is evaluating solengepras as an adjunctive therapy to levodopa and other background PD medications in a different patient population than ASCEND.

Opdenakker adds: “As a monotherapy, solengepras’ would struggle to find a niche, as it would face competition from well-established therapies for the treatment of core PD symptoms, such as levodopa, dopamine agonists (DAs), and monoamine oxidase B inhibitors (MAO-Bs).”

According to GlobalData’s Drugs Database, six dopamine agonists are currently marketed across the seven major pharmaceutical markets (7MM: The US, France, Germany, Italy, Spain, UK, and Japan), many of which are available as generics. Additionally, AbbVie’s tavapadon is another DA that is in Phase III development.

Given the crowded market, it will be difficult for solengepras to compete directly with the other DAs already on the market as a monotherapy, so entering the market as an adjunctive therapy would be the most likely route to success.

The key opinion leaders (KOLs) previously interviewed by GlobalData have noted that dopamine agonists are no longer the preferred adjunctive therapies for PD due to side effects such as hallucinations, delusions, and compulsive behavior. As a GPR6 antagonist, solengepras has a novel, potentially first-in-class, non-dopaminergic mechanism, which differentiates it from competitors.

However, the adjunctive treatment space is also competitive. Cerevance will need to demonstrate superior efficacy and safety over marketed adjunctive therapies in large Phase III clinical trials or engage in head-to-head studies to effectively compete.

Opdenakker concludes: “Solengepras demonstrated promising trends in improving non-motor symptoms and functional impairments. Furthermore, its favorable safety profile, novel mechanism of action, and promising data when investigated as an adjunctive treatment, have indicated that it is a potentially valuable adjunctive therapy. Pending the results of the Phase III ARISE trial, solengepras could be an option as an adjunctive therapy for PD patients with motor function.”