HQ Team
March 17, 2025: Celon Pharma’s human trial with PDE10A inhibitor, CPL’36, has achieved statistically significant reductions in involuntary movements caused by levodopa used by Parkinson’s disease patients.
The study met its primary endpoint and most secondary endpoints, positioning the drug as a potential breakthrough for levodopa-induced dyskinesia (LID), a common and debilitating side effect of long-term Parkinson’s treatment.
In Parkinson’s dopamine levels are reduced. Dopamine is a neurotransmitter hormone that plays a role as a “reward center” and in many body functions, including memory, movement, motivation, mood, and attention.
Levodopa, or L-DOPA, is commonly used to treat PD symptoms. The precursor to dopamine, it crosses the blood-brain barrier and is converted to dopamine inside the brain, helping restore movement.
Unfortunately, in around 80% of people with PD, its long-term use causes levodopa-induced dyskinesia (LID), a condition characterized by uncontrolled jerking, writhing, or fidgeting.
Trial
CPL’36 is a novel, oral, once-daily medication for the treatment of Levodopa-Induced Dyskinesia (LID) in Parkinson’s disease, and it demonstrated robust and consistent efficacy across all utilized scales measuring improvement in the treatment of LID in Parkinson’s disease. The effect size was large and clinically meaningful. CPL’36 was previously investigated as a potential treatment for schizophrenia and demonstrated positive Phase 2 results that were reported in July 2024.
For the trial 105 patients receiving 20 mg and 40 mg doses showed improvements of 12.3 units (p < 0.001) and 13.58 units (p < 0.001), respectively, on the Unified Dyskinesia Rating Scale (UDysRS), with large effect sizes (Cohen’s d: 0.90–1.00). The UDysRS measures the severity of LID. The total score ranges from zero to 104, with higher scores indicating greater severity or disability.
The 20 mg cohort reported no severe adverse events (AEs), compared to 5.7% in the 40 mg group and 8.8% in placebo. Discontinuation rates due to AEs were 11.1% (20 mg), 8.6% (40 mg), and 2.9% (placebo).
Celon CEO Maciej Wieczorek, Ph.D., highlighted the drug’s potential to address unmet needs for LID patients, stating, “The results are unequivocally positive, clinically meaningful, and statistically significant”. The company plans to advance CPL’36 into registrational trials after discussions with global regulators.
Broader potential
CPL’36’s rapid enzyme dissociation profile distinguishes it from other PDE10A inhibitors, a feature linked to its efficacy, according to Joanna Sierzputowska-Prarat, Celon’s neuropsychiatry lead.
While Celon progresses, rivals like Noema Pharma and EuMentis Therapeutics are also pursuing PDE10A inhibitors. Noema’s gemlapodect reduced tic severity in Tourette syndrome, while EuMentis aims for a Phase 2 Parkinson’s trial in early 2025.
Celon intends to expand its Parkinson’s disease portfolio, leveraging CPL’36’s dual potential in LID and schizophrenia. With over 24 million schizophrenia patients globally and a growing Parkinson’s population, the drug could tap into multibillion-dollar markets if approved.
