Solengepras significantly reduces off time for patients on levodopa
Daily oral pill keeps symptoms at bay when levodopa wears off: Phase 2 trial
- Solengepras, an experimental oral pill, significantly reduces Parkinson's off episodes.
- Off episodes are re-emerging motor symptoms in Parkinson's patients on levodopa.
- This once-daily pill targets GPR6, with a Phase 3 trial currently underway.
Solengepras, an experimental once-daily pill for Parkinson’s disease, significantly reduces the time patients spend with re-emerging symptoms, known as off episodes.
New Phase 2 data suggest the treatment reduces both the frequency and length of these difficult periods when standard medication wears off.
The trial (NCT04191577) tested the treatment in 110 patients with at least two hours of off episodes, who received once-daily doses of solengepras or a placebo for approximately one month. Data were presented at the 2025 Parkinson Study Group annual meeting, held recently in San Diego, in a poster presentation titled “Characteristics of OFF time Improvement in a Phase 2 Study for Parkinson’s Disease (PD) with Solengepras, a Novel GPR6-inhibitor.”
A pivotal Phase 3 ARISE trial (NCT06553027) is currently recruiting patients at sites in the U.S. and Australia. It is evaluating the efficacy of solengepras as a potential once-daily add-on therapy to other Parkinson’s medications. The trial began dosing patients last year, with topline data expected in 2026.
Impact of off episodes and current treatments
“These off episodes, which can cause a return of Parkinson’s motor symptoms, can be very disabling,” Harini Sarva, MD, trial investigator and an associate professor at Weill Cornell Medicine, in New York, said in a press release. “The significant and clinically meaningful reductions in off time observed with solengepras highlight the potential of this once-daily, oral treatment to improve quality of life.”
Parkinson’s disease is caused by the progressive loss of dopaminergic neurons, the nerve cells responsible for producing dopamine, a neurotransmitter crucial for motor control. Levodopa, a dopamine precursor, is the standard of care for easing the motor symptoms of the disease, including tremors, stiffness, and slowed movements.
However, long-term use of levodopa may lead to off periods, when symptoms are not adequately controlled with the medication, and sudden and uncontrolled movements, called dyskinesia, appear.
“More than 90% of individuals with Parkinson’s disease who have received carbidopa/levodopa therapy for over 5 years experience motor fluctuations, including daily off time,” Sarva said.
Solengepras, developed by Cerevance, is specifically designed to target and block GPR6, a protein receptor found in specific nerve cells within the striatum, which is a region crucial for controlling voluntary movement. The treatment is expected to produce effects similar to those of levodopa, without affecting dopamine levels, thereby reducing off episodes and dyskinesia.
The presented Phase 2 data show that patients receiving 150 mg of solengepras experienced a statistically significant average reduction of 1.3 hours in total daily off time compared with those on the placebo.
Among the subgroup of patients with at least three hours of daily off time (88% of participants), off time decreased by 1.78 hours, representing a 34.7% reduction. The treatment also cut the number of daily off episodes by nearly one episode and shortened each episode by an average of 26 minutes.
Solengepras showed a favorable safety profile, marked by a low incidence of adverse events.
“These data reinforce solengepras’ potential as a differentiated, non-dopaminergic approach,” said Craig Thompson, Cerevance’s CEO. “With the Phase 3 ARISE trial now underway, we are one step closer to bringing this treatment option to patients in need.”
The ongoing Phase 3 trial is enrolling up to 330 patients who experience three or more hours of off time per day. Participants will receive one of two doses of solengepras (75 or 150 mg) or a placebo once daily, in combination with levodopa. The trial will evaluate the treatment’s effectiveness in reducing off time, increasing good on time — when symptoms are well-controlled without dyskinesia — and its effects on nonmotor symptoms and patients’ quality of life. As a pivotal trial, it is designed to provide evidence to support a regulatory submission seeking therapy approval.
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