- Solengepras showed evidence of potential benefit in functional and non-motor symptoms versus placebo as measured by MDS-UPRDS Parts I, II, NMSS, and ESS, consistent with its novel non-dopaminergic mechanism of action
- This investigational treatment was generally well tolerated with no serious adverse events; fewer adverse events related to non-motor symptoms were reported in the solengepras arm
- Pivotal Phase 3 ARISE trial evaluating solengepras as adjunctive therapy in Parkinson’s disease is ongoing with topline data expected in first half of 2026
BOSTON, April 01, 2025 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, today announced topline results from the Phase 2 ASCEND trial of solengepras as an investigational monotherapy in patients with early, untreated Parkinson’s disease. The data was presented today in the “Advances in PD” Symposium session at AD/PD™ 2025, the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, in Vienna.
Solengepras, the most advanced investigational treatment in Cerevance’s pipeline, is an oral, non-dopaminergic therapy in Phase 3 development for Parkinson’s disease. A brain-penetrant, specific inhibitor of GPR6, solengepras is designed to selectively target and modulate the specific brain circuits responsible for controlling motor and non-motor functions without directly affecting dopaminergic pathways. This novel mechanism of action is designed to reduce motor complications such as dyskinesia, minimize periods of symptomatic worsening (“OFF” time), and improve non-motor symptoms.
In the ASCEND trial, solengepras showed a small, non-statistically significant improvement in Parkinson’s disease motor symptoms from baseline to week 12 compared to placebo as assessed by the combined Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II+III. Those results were not statistically significant primarily because of the lack of differentiation between solengepras and placebo in the Part III physician-administered neurological exam, which assesses the physical signs of Parkinson’s disease at a single point in time.
Trends in improvement were observed for several other patient-reported measures. Those included the MDS-UPDRS Part I (-1.38, p=0.12), the MDS-UPDRS Part II (-0.4, p=0.62), the Non-Motor Symptoms Scale (-1.7, p=0.59), and the Epworth Sleepiness Scale (-0.3, p=0.62), indicating potential benefit in both functional and non-motor aspects of Parkinson’s disease.
Solengepras was well tolerated, with 100% of patients in the treatment arm completing the 12-week trial and no discontinuations due to a study-drug related adverse event (AE). No serious AEs related to solengepras were reported, and the majority of AEs were mild and transient. Notably, fewer AEs related to non-motor symptoms were reported in the treatment arm than in the placebo arm.
"For people with Parkinson’s disease, dopaminergic therapies are the standard of care as they reduce tremors, stiffness, slowed movement, and other symptoms. However, there are crucial treatment gaps in addressing functional impairments and non-motor symptoms," said Aaron L. Ellenbogen, D.O., M.P.H., primary investigator of the ASCEND trial, assistant professor of medicine at Oakland University William Beaumont School of Medicine, and neurologist at the Parkinson’s Disease & Movement Disorders Center at the Michigan Institute for Neurological Disorders. "The improvements in functional and non-motor symptoms observed in the patient-reported measures of the ASCEND trial suggest that solengepras could be a promising option for managing non-motor symptoms without the distressing side effects associated with conventional dopaminergic therapies."
“We are encouraged by the results of the Phase 2 ASCEND trial of solengepras as a monotherapy, which align with findings from our Phase 2 trial of solengepras as an adjunctive therapy, with both demonstrating benefits on patient-reported measures,” said Craig Thompson, chief executive officer of Cerevance. “The ASCEND data further reinforces that solengepras, with its novel, non-dopaminergic mechanism, appears to be more effective in impacting the functional and non-motor symptoms captured by patient-reported outcomes, which are generally considered more meaningful for patients. Given the treatment gaps in addressing these symptoms, solengepras has the potential to fill a critical unmet need in Parkinson’s disease care.”
About the Phase 2 ASCEND Trial
The multicenter, randomized, double-blind, placebo-controlled Phase 2 ASCEND (A novel Selective Compound to ENable Individuals with Parkinson’s Disease) evaluated the efficacy and safety of solengepras in patients with early Parkinson’s disease who have not been treated with dopaminergic or anti-Parkinson’s therapies. A total of 64 patients age 30 and older were randomized to solengepras 150 mg daily or placebo for 12 weeks. The primary endpoint was change from baseline to week 12 on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II+III. Key secondary endpoints included MDS-UPDRS Parts I-III, the Non-motor Symptoms Scale (NMSS), the Epworth Sleepiness Scale (ESS), and safety. ASCEND was conducted at sites in the United States.
About Solengepras (formerly CVN424)
Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as an adjunctive therapy to levodopa and other anti-Parkinsonian medication in the Phase 3 ARISE trial.
About the Pivotal Phase 3 ARISE Trial
The multicenter, randomized, double-blind, placebo-controlled Phase 3 ARISE trial is evaluating the efficacy and safety of solengepras as an adjunctive therapy to levodopa and other background Parkinson’s disease medications. The trial is enrolling approximately 330 patients with Parkinson’s disease age 30 and older with motor fluctuations who have an average of three or more hours of total “OFF” time per day. Study participants are randomized to solengepras 75 mg or 150 mg or placebo once daily for 12 weeks. The primary endpoint is the change from baseline to week 12 in average daily “OFF” time for solengepras 150 mg versus placebo. Secondary objectives include assessing safety and tolerability and further characterizing the effect of solengepras on other motor symptoms (e.g., ON time), non-motor symptoms (e.g., daytime sleepiness), cognitive function, and several quality-of-life measures (e.g., Movement Disorder Society-UPDRS, PD Questionnaire 39, Clinical Global Impression scale, Patient Global Impression scale). ARISE is being conducted globally at sites in the United States and Europe.
About Parkinson’s Disease
Parkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorder, affecting more than 10 million people worldwide and approximately 1 million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, such as levodopa, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit profiles.
About Cerevance
Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders. Our proprietary platform, Nuclear Enriched Transcript Sort sequencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced investigational treatment, solengepras, is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both motor and non-motor symptoms of Parkinson's disease. Our second investigational therapy, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor for the potential treatment of binge eating disorder and schizophrenia. Our third investigational treatment, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13). CVN293 represents a potentially novel intervention point for neurodegenerative disorders and obesity. For more information, please visit www.cerevance.com and follow us on LinkedIn and X.
Contacts
Cerevance:
Johnna Simoes, ir@cerevance.com
Media
April Dovorany, adovorany@realchemistry.com, +1-262-909-8739
