A tablet taken once a day has just shown positive results in 341 people with Parkinson’s disease in an international Phase 3 trial. Behind these figures stands the first major family of drugs announced in decades. Dame Kate Bingham, Managing Partner at SV Health Investors, talks about a “Completely new class of drugs beyond the dopamine pathway, which has been the mainstay of Parkinson’s disease treatment for decades“.
This drug candidate is called solengepras
(CVN424) and it is developed by the American biotech Cerevance as a non-dopaminergic oral tablet, to be taken once a day in addition to levodopa. In the ARISE trial, the 150 mg dose reduced the average “OFF” time by 0.61 hours per day compared to placebo, with an effect visible from the second week, and also increased the “ON” time without bothersome dyskinesia. For patients, that’s about 37 fewer minutes spent each day with stiffness, slowness and tremors.
How solengepras works in Parkinson’s disease
“Parkinson’s disease has many repercussions on the quality of life of those affected, particularly on their movements, causing tremors, slowness and stiffness. There is currently no cure, and as the disease progresses, standard treatments may become less effective in controlling symptoms, leading to motor fluctuations: unpredictable variations between good and poor symptom control throughout the day. says Dr Mubasher Qamar, clinician and senior researcher in movement disorders and neurology at King’s College London.
THE solengepras is a selective inhibitor of the GPR6 receptor, located in the so-called indirect pathway of the basal ganglia, which controls movements. Unlike current treatments focused on dopamine such as levodopa, it does not replace this chemical messenger and does not bind to its receptors: it seeks to rebalance the circuits by releasing a “brake” that becomes too powerful when the dopamine-producing neurons disappear. An international phase 3 study, called ARISE, recruited 341 participants in the United States, Europe, the United Kingdom and Australia. It aims to demonstrate whether solengepras (CVN424) could potentially improve motor fluctuations and help affected people better control their symptoms.
In ARISE, this mechanism was tested only in combination, in adults aged 30 and over who had at least three hours of OFF time per day despite their treatments, with an average of 5.65 hours per day where symptoms returned. ON and OFF phases refer to fluctuations in the effectiveness of dopaminergic treatment throughout the day in people with Parkinson’s disease. This phenomenon generally appears after several years of progression of the disease.
ARISE trial: what the daily tablet changes for patients
The 341 people with Parkinson’s were randomly divided into three groups receiving 75 mg, 150 mg or a placebo for 12 weeks, in addition to their usual treatments.
- At the end of the study, according to Cerevance, the 150 mg dose reduced OFF time by 1.56 hours compared to the start, compared to 0.95 hours in the placebo group, or 0.61 hours saved in addition, approximately 37 minutes per day, with an effect visible from the second week;
- ON time without bothersome dyskinesia increased by 1.58 hours in the 150 mg group compared to 0.98 hours on placebo, the MDS-UPDRS Part II scale improved further, as did daytime sleepiness and quality of life (PDQ-39 questionnaire).
“In the ARISE study, patients treated with solengepras spent less time in the OFF phase and also reported improvements in their daily activities. Improvements were also observed in quality of life and daytime alertness.said Dr. Robert A. Hauser, principal investigator of the trial and director of the Center for Movement Disorders and Parkinson’s Disease at the University of South Florida, as well as professor of neurology at the same university’s School of Medicine. “OFF time has long been the main criterion for evaluating adjunctive treatments, but it only reflects one aspect of the disease. The joint analysis of these measures could make it possible to more fully understand the potential benefits of a treatment for patients..
The success of ARISE comes after a contrasting journey: in 2025, a Phase 2 study where solengepras was given alone to newly diagnosed patients had not achieved its main objective on motor symptoms, while another Phase 2 trial as an adjunctive treatment had already shown a reduction in OFF time.
A new class of treatment still awaiting green light
Cerevance now plans to discuss these results with the FDA to define the possible submission of an authorization file, but solengepras remains for the moment a drug in development, not available outside of clinical trials.