Non-dopamine Parkinson's pill trims daily OFF time in a big trial

A once-daily pill that works without acting on dopamine has reduced the hours people with Parkinson's spend in poorly controlled "OFF" periods, according to topline results from the phase 3 ARISE trial.

Solengepras, made by Boston company Cerevance, cut daily OFF time by 0.61 hours more than placebo after 12 weeks at the 150 mg dose. It also improved daily motor function, daytime sleepiness and quality of life, with few of the side effects common to dopamine drugs.

The results were announced on 7 October 2026 and presented at the International Congress of Parkinson's Disease and Movement Disorders (MDS Congress) in Seoul by Dr Robert Hauser of the University of South Florida and Dr Karl Kieburtz, chief medical officer of Cerevance. The presentation was scheduled at 08:00 Seoul time (01:00 in Madrid). The findings have not yet been published in a peer-reviewed journal.

OFF time in Parkinson's

Parkinson's disease is caused by the loss of dopamine-producing nerve cells in a part of the brain called the substantia nigra. It causes slowness, stiffness and tremor, along with non-motor problems such as sleepiness, low mood, constipation and changes in thinking.

Levodopa, which the brain converts to dopamine, remains the most effective treatment. Over the years, though, many people develop motor fluctuations. Each dose works for a shorter time, and symptoms return before the next one is due. These periods of returning symptoms are called OFF time.

Doctors add other medicines to smooth out the day. Most of them, such as dopamine agonists and MAO-B or COMT inhibitors, work through the dopamine system. They can bring side effects such as dyskinesia (involuntary movements), hallucinations, sleepiness and impulse control problems.

A different target

Solengepras targets GPR6, a receptor found almost only on a group of nerve cells in the striatum that form what is called the indirect pathway. In Parkinson's, low dopamine makes this pathway overactive, which acts as a brake on movement. Blocking GPR6 is meant to ease that brake without stimulating dopamine receptors directly.

Cerevance calls it a potential first-in-class treatment. If approved, it would be the first Parkinson's medicine to work through GPR6.

The ARISE trial

ARISE (NCT06553027) was a randomised, double-blind, placebo-controlled phase 3 trial. It enrolled people with Parkinson's who had motor fluctuations despite levodopa and other medicines, which they continued throughout.

According to Cerevance, 341 participants were randomised in equal numbers to:

• Solengepras 75 mg once daily (114 people)
• Solengepras 150 mg once daily (113 people)
• Placebo (114 people)

Treatment lasted 12 weeks. At the start, participants had an average of 5.65 hours of OFF time a day. In all, 311 of the 341 (91%) completed the trial.

The main measure was change in daily OFF time, recorded in patient diaries, at week 12.

What the trial found

At 150 mg, solengepras met the main goal. Daily OFF time fell by 1.56 hours from the start, against 0.95 hours with placebo. The difference of 0.61 hours (about 37 minutes) was statistically significant (p=0.0350).

The difference appeared early. At week 2, the first check, OFF time was 0.75 hours lower than placebo (nominal p=0.0022), and the benefit was seen at every visit through week 12.

On the key secondary goals at 150 mg:

• ON time without troublesome dyskinesia rose by 0.60 hours more than with placebo (1.58 against 0.98 hours; p=0.0468).
• Motor experiences of daily living, measured by part II of the MDS-UPDRS rating scale, improved by 1.91 points more than with placebo (2.05 against 0.14; p=0.0008).

Two non-motor measures also improved:

• Daytime sleepiness on the Epworth Sleepiness Scale improved by 0.98 points against placebo (nominal p=0.009).
• Quality of life on the PDQ-39, an exploratory measure, improved by 2.87 points (nominal p=0.012).

Cerevance did not report detailed results for the 75 mg dose in its announcement.

Side effects

Most side effects were mild or moderate, according to Cerevance. Stopping because of an adverse event happened in 3.5% of each group, including placebo. There were no serious adverse events with 150 mg, against 1.8% with 75 mg and 0.9% with placebo.

The most common side effects at 150 mg were:

The company said the low rate of typical dopamine-related side effects may fit with the drug's mechanism.

How big is the benefit

A reduction in OFF time of about 37 minutes a day against placebo is modest. A large placebo response is typical in OFF-time trials, and the placebo group here improved by almost an hour.

The gain in daytime alertness stands out, because many existing add-on drugs make sleepiness worse. The improvement in daily-living scores also suggests that the change was noticeable to patients. Several non-motor results were only nominal or exploratory, though, and need confirming.

What the investigators said

"In ARISE, patients receiving solengepras spent less time 'OFF' and also reported improvements in everyday functioning. Improvements were also observed in quality of life and daytime alertness," said Dr Hauser. "OFF time has long been the main way we assess add-on therapies, but it captures only one aspect of the disease."

Craig Thompson, chief executive of Cerevance, said the company looked forward to discussing the results with the FDA to determine next steps.

Other new Parkinson's drugs

ARISE arrives as Parkinson's treatment options are changing. According to CT Analytics, the FDA approved tavapadon (Juvmo, AbbVie) on 28 September 2026, the first selective D1/D5 dopamine receptor agonist. Solengepras takes a different route altogether by avoiding dopamine receptors.

Limits of the evidence

• These are topline data from a company announcement and conference presentation. Full results have not been peer reviewed.
• The trial lasted 12 weeks. Longer-term benefit and safety are unknown.
• Only the 150 mg dose met the main goal in the reported data.
• The p-value for the main result (0.035) is significant but not large, and some secondary findings are nominal.
• Cerevance funded the trial.

What it means for people with Parkinson's

Solengepras is not approved anywhere. Cerevance plans to meet the FDA to discuss a possible marketing application. People with Parkinson's who have OFF periods should keep taking their current medicines and talk to their neurologist or Parkinson's nurse about options.

This article explains published research and isn't medical advice. Talk to your own doctor or specialist team before changing any treatment.