Dosing begins in Phase 3 trial of Parkinson's therapy solengepras

21 Nov 2024, 13:00 by Andrea Lobo · Parkinson's News Today

A Phase 3 clinical trial evaluating investigational oral therapy solengepras as a treatment for Parkinson’s disease has dosed its first patient.

The ARISE trial (NCT06553027) is evaluating the efficacy of solengepras as a potential add-on therapy to levodopa and other Parkinson’s medications. Patient recruitment is ongoing at several sites in the U.S.

Cerevance, the company’s developer, expects topline data from the trial in the first half of 2026.

“The initiation of ARISE builds on the encouraging Phase 2 data we have generated and represents an exciting chapter in Cerevance’s journey to address the unmet needs of individuals with Parkinson’s disease,” Sagar Vaidya, MD, PhD, chief medical officer at Cerevance, said in a company press release.

Parkinson’s disease is caused by the degeneration of dopaminergic neurons, the nerve cells that produce dopamine, a brain chemical messenger essential for regulating muscle movement. Levodopa, a dopamine precursor, is considered the mainstay treatment for Parkinson’s.

Parkinson’s therapy side effects

Long-term treatment with levodopa may cause unwanted side effects such as dyskinesia, or sudden, uncontrolled movements. As the disease progresses, patients may experience periods when symptoms are not effectively managed by the prescribed medication, called off periods.

Solengepras, also known as CVN424, is a small molecule that is able to enter the brain and block GPR6, a protein receptor produced by a type of nerve cells in the striatum, a brain region critical for motor control. By suppressing GPR6, solengepras is expected to lead to beneficial effects similar to levodopa while minimizing side effects such as dyskinesia.

“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, Cerevance’s CEO.

The treatment, Thompson said, “is designed to reduce motor complications such as dyskinesia and “OFF” periods, which we believe may offer potentially improved tolerability and potential impact on non-motor symptoms for individuals with Parkinson’s disease.”

In a previous Phase 2 trial (NCT04191577) that enrolled Parkinson’s patients on a consistent dose of levodopa and other anti-parkinsonian medications, solengepras significantly reduced off time and increased on time, or periods when symptoms are well controlled, without dyskinesia.

The treatment was also well tolerated, with no reported serious treatment-related adverse events.

The ARISE trial plans to enroll 330 Parkinson’s patients aged 30 and older, with three or more hours per day of off time, who will receive one of two doses of solengepras (75 or 150 mg) or a placebo, once daily. All participants will also be actively treated with levodopa.

The trial’s main goal is to assess changes in daily off time after 12 weeks of treatment. Secondary measures include changes in on time without troublesome dyskinesia, 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, and behavioral issues, as well as the incidence of treatment-related and serious adverse events.

Participants who successfully finish this trial and remain eligible can join a follow-up study in which all participants receive solengepras.

“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,” Vaidya said.

Solengepras is also being tested as a single therapy in the Phase 2 ASCEND clinical trial (NCT06006247), in patients with early, not previously treated Parkinson’s disease.