New study shows promise of Risvodetinib for early Parkinson’s disease

Risvodetinib, a potential c-Abl inhibitor, recently underwent a phase 2 trial for early Parkinson disease (PD), demonstrating encouraging signs of functional improvement and potential disease-modifying effects. The study was a 12-week, double-blind, placebo-controlled trial evaluating three different once-daily oral doses of risvodetinib—50 mg, 100 mg, and 200 mg—in individuals with early-stage PD who had not yet been treated with dopaminergic therapy. The results of this trial were presented at the 2025 International Congress of Parkinson’s Disease and Movement Disorders in Honolulu, Hawaii.

According to Milton Werner, PhD, the founder and CEO of ABLi Therapeutics, and his colleagues, the trial met its primary safety and tolerability endpoints and showed promising functional and pathologic improvement signals in patients with early PD. Secondary efficacy outcomes focused on assessing motor and nonmotor symptoms using validated scales, with the 100-mg and 50-mg doses showing nominal statistical significance in improving these symptoms. Additionally, there was an observed dose-response trend on the MDS-UPDRS Part 2, indicating a potential relationship between the drug dosage and symptom improvement. Overall, 13 out of 15 secondary outcome assessments favored risvodetinib over the placebo, suggesting its potential benefits.

Notably, 95% of the participants completed the full 12-week regimen, with risvodetinib showing good tolerability and safety among the majority of patients. Adverse events were generally mild to moderate and occurred at similar rates to those seen with the placebo. Exploratory biomarker data revealed a dose-dependent reduction in alpha-synuclein deposition, pointing towards a potential disease-modifying effect of the drug. These findings align with previous preclinical data that linked c-Abl inhibition to the clearance of pathological alpha-synuclein aggregates, further supporting the potential of risvodetinib in treating PD.

Although the trial was not specifically designed to demonstrate definitive efficacy on clinical outcomes, the consistent improvements in both motor and nonmotor symptoms, along with the observed safety profile and reduction in alpha-synuclein burden, suggest that risvodetinib warrants further investigation as a potential disease-modifying therapy for PD. A larger phase 3 trial is anticipated to assess clinical efficacy, durability of response, and confirm the drug’s impact on alpha-synuclein burden.

Overall, the phase 2 trial for risvodetinib in early PD has shown promising results, paving the way for further research and development of this drug as a potential treatment for Parkinson’s disease.