Phase 3 Trial of Solengepras for Parkinson's Disease Begins Dosing
核心洞察
Cerevance (搜索)'s solengepras, an oral GPR6 (搜索) inhibitor, has entered a Phase 3 clinical trial (ARISE) as an add-on therapy for Parkinson's disease (搜索).
The ARISE trial (NCT06553027) will evaluate solengepras' efficacy in reducing off-time in Parkinson's patients already treated with levodopa.
Solengepras aims to improve motor control and reduce dyskinesia (搜索) by modulating brain circuits without directly relying on dopamine pathways.
The first patient has been dosed in a Phase 3 clinical trial evaluating solengepras, an investigational oral therapy, for the treatment of Parkinson's disease (搜索). The ARISE trial (NCT06553027) is assessing the efficacy of solengepras as an add-on therapy to levodopa and other Parkinson's medications. Patient recruitment is currently underway at multiple sites across the U.S., with topline data expected in the first half of 2026.
Targeting Motor Complications in Parkinson's
Parkinson's disease (搜索) results from the degeneration of dopaminergic neurons, which produce dopamine, a crucial neurotransmitter for regulating movement. Levodopa, a dopamine precursor, remains the primary treatment; however, long-term use can lead to side effects like dyskinesia (搜索) and "off" periods, where symptoms are not effectively managed.
Solengepras, also known as CVN424, is a small molecule designed to cross the blood-brain barrier and block GPR6 (搜索), a protein receptor produced by nerve cells in the striatum, a brain region critical for motor control. By inhibiting GPR6, solengepras aims to provide benefits similar to levodopa while minimizing side effects such as dyskinesia (搜索).
Novel Mechanism of Action
"Unlike traditional Parkinson's treatments that aim to restore dopamine levels, solengepras is designed to selectively target and modulate the specific brain circuits responsible for controlling movement and non-motor functions, without relying directly on dopamine pathways," said Craig Thompson, CEO of Cerevance (搜索).
The treatment is designed to reduce motor complications such as dyskinesia (搜索) and "OFF" periods, potentially offering improved tolerability and impacting non-motor symptoms for individuals with Parkinson's disease (搜索).
Phase 2 Trial Results
In a previous Phase 2 trial (NCT04191577), solengepras significantly reduced off time and increased on time without troublesome dyskinesia (搜索) in Parkinson's patients on a stable dose of levodopa and other anti-parkinsonian medications. The treatment was also well-tolerated, with no serious treatment-related adverse events reported.
ARISE Trial Design
The ARISE trial plans to enroll 330 Parkinson's patients aged 30 and older, experiencing three or more hours per day of off time. Participants will receive one of two doses of solengepras (75 or 150 mg) or a placebo, once daily, in addition to their existing levodopa treatment.
The primary endpoint of the trial is the change in daily off time after 12 weeks of treatment. Secondary endpoints include changes in on time without troublesome dyskinesia (搜索), as measured by the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and patient and clinician-reported scales of disease severity. The trial will also assess changes in patients’ health-related quality of life, cognitive function, sleepiness, apathy, behavioral issues, and the incidence of treatment-related adverse events.
Participants who complete the trial and remain eligible may enroll in a follow-up study where all participants receive solengepras.
Future Directions
"We look forward to advancing solengepras through this pivotal trial and moving closer to potentially bringing a new, non-dopaminergic therapy to the Parkinson’s community," said Sagar Vaidya, MD, PhD, chief medical officer at Cerevance (搜索).
Solengepras is also being investigated as a monotherapy in the Phase 2 ASCEND clinical trial (NCT06006247) in patients with early, previously untreated Parkinson’s disease.