Once-daily treatment may reduce Parkinson’s off time, study finds

The 150 mg dose of solengepras (CVN424), Cerevance’s investigational oral treatment for Parkinson’s disease, significantly reduced average daily off time — periods when symptoms reappear despite medication — compared with placebo, according to topline results from a Phase 3 trial.

The Phase 3 ARISE trial (NCT06553027) evaluated the safety and efficacy of solengepras in addition to standard treatments in people with Parkinson’s disease who experience motor fluctuations. The trial enrolled 341 participants at sites worldwide, completing enrollment earlier this year.

“ARISE met its primary endpoint and showed a consistent pattern of benefit across OFF time, ON time, daily motor function, daytime alertness and quality of life, together with favorable tolerability,” Craig Thompson, Cerevance’s CEO, said in a company press release. “We look forward to discussing these results with the FDA to determine next steps.”

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How solengepras may help control Parkinson’s motor symptoms

Parkinson’s disease is caused by the loss of nerve cells that produce dopamine, a chemical messenger that helps control movement. Levodopa, which the brain converts into dopamine, is a standard treatment for easing Parkinson’s motor symptoms. However, long-term use of levodopa can lead to off periods and dyskinesia, or sudden, involuntary movements.

Solengepras is designed to block GPR6, a receptor found on specific nerve cells in the striatum, a brain region involved in controlling voluntary movement. By blocking GPR6, solengepras is designed to help restore balance between brain pathways involved in movement without directly altering dopamine levels or signaling.

The ARISE trial evaluated once-daily solengepras at 75 or 150 mg versus placebo in people with Parkinson’s who averaged at least three hours of off time per day despite treatment with levodopa and other Parkinson’s medications.

According to the company, the 150 mg dose met the trial’s primary goal, significantly reducing average daily off time by 0.61 hours, or about 37 minutes, versus placebo at Week 12. A difference between the treatment and placebo groups was seen as early as Week 2, the first assessment after treatment began, and at each subsequent visit through Week 12.

The 150 mg dose also increased on time without troublesome dyskinesia by 36 minutes versus placebo.

The 150 mg dose also significantly improved motor experiences of daily living, with a 1.91-point improvement versus placebo, as measured by Part 2 of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale. Participants receiving the 150 mg dose also had less daytime sleepiness on a secondary measure and better quality of life on an exploratory measure.

150 mg dose improved motor and non-motor measures

“OFF time has long been the main way we assess add-on therapies, but it captures only one aspect of the disease. Looking at these measures together may give a fuller picture of a treatment’s potential benefits for patients,” said Robert A. Hauser, MD, trial investigator and professor at the University of South Florida.

Solengepras was generally well tolerated, with most adverse events mild or moderate. The most common adverse events with the 150 mg dose were headache and urinary tract infection (8% each), followed by insomnia and nausea (6.2% each). Dyskinesia was reported in 4.4% of participants receiving 150 mg solengepras, compared with 1.8% of those receiving placebo.

Treatment was discontinued because of an adverse event in 3.5% of participants in each group, including placebo. No serious adverse events were reported among those receiving the 150 mg dose, compared with 1.8% among those receiving 75 mg and 0.9% among those receiving placebo.

“As a potential first-in-class, non-dopaminergic therapy, solengepras gives us the opportunity to evaluate what a new mechanism may offer people with Parkinson’s and ARISE was designed to capture that full picture,” Thompson said.