Risvodetinib, an investigational c-Abl inhibitor, met its primary safety and tolerability end points and showed promising signals of functional and pathologic improvement in a 12-week, phase 2 study of patients with early and untreated Parkinson disease (PD).1 The multicenter, double-blind, placebo-controlled 201 Trial (NCT05424276) evaluated 3 once-daily oral doses of risvodetinib—50 mg, 100 mg, and 200 mg—in individuals with early-stage PD who had not yet initiated dopaminergic therapy.
The data were presented at the
Secondary efficacy outcomes assessed motor and nonmotor symptoms using a range of validated scales. Two measures—MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 2 and the Schwab and England Activities of Daily Living (SEADL) scale—reached nominal statistical significance at the 100-mg and 50-mg doses, respectively. An approximate dose-response trend was observed on Part 2 of the MDS-UPDRS. Across the 15 secondary outcome assessments, 13 showed a numerical trend favoring risvodetinib over placebo.
In total, 95% of the enrolled participants completed the full 12-week regimen, and risvodetinib was generally well tolerated, with mild to moderate adverse events occurring at a frequency and severity comparable to placebo.
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Exploratory Findings for Risvodetinib
Additionally, exploratory biomarker data revealed a dose-dependent reduction in cutaneous neuronal alpha-synuclein deposition in a subset of patients, suggesting a potential disease-modifying effect. This reduction aligns with the hypothesized mechanism of action of risvodetinib and supports earlier preclinical findings that linked c-Abl inhibition with clearance of pathological alpha-synuclein aggregates.
While the trial was not powered to demonstrate definitive efficacy on clinical outcomes, the consistency of motor and nonmotor improvements, combined with the safety profile and reduction in alpha-synuclein, supports continued investigation of risvodetinib as a potential disease-modifying therapy for PD, according to Werner and colleagues. A larger, longer-term phase 3 trial is likely to further assess clinical efficacy and durability of response, as well as confirm the drug’s effect on alpha-synuclein burden.
Prior Risvodetinib Data Announcements
Previously, at the 2024 AD/PD Meeting, held March 5-9, in Lisbon, Portugal, Inhibikase presented an update on the phase 2 study, Trial 201 (NCT05424276), of risvodetinib in PD, which included 25 participants who had completed the 12-week treatment period.3 The trial completed enrollment in June 2024.
In a Securities and Exchange Commission filing in early 2025, Inhibikase revealed that while risvodetinib had hit its safety and tolerability primary end point in untreated PD, it had failed to reach the same goals when it came to efficacy, noting that “risvodetinib treatment did not demonstrate an improvement in the top hierarchical efficacy measure, which was the sum of Parts 2 and 3 of the [MDS-UPDRS] at any dose group (50 mg, 100 mg or 200 mg) versus placebo.”4