Objective: To compare the clinical efficacy of two catechol-O-methyltransferase (COMT) inhibitors, opicapone (OPC) and entacapone (ENT).

Background: OPC and ENT are used as adjunctive therapy to levodopa (LD) to improve the bioavailability of LD and reduce peak-trough fluctuations.

Method: BIPARK I was a multicenter, double-blind (DB), 14- to 15-week, placebo-controlled, active-controlled (ENT) phase 3 study, followed by a 1-year open-label extension (OLE) study to evaluate the treatment effect of OPC in patients with Parkinson’s disease (PD) and motor fluctuations. A review of efficacy data of BIPARK I and subanalysis of the OLE study was conducted.

Results: BIPARK I established the noninferiority of OPC 50mg vs ENT 200mg. Moreover, it demonstrated OPC’s effectiveness in reducing “Off” time, with greater magnitude of reduction in time in “Off” state vs ENT (LS mean change of -116.8min vs -96.3min, respectively), offering potential advantages over the multiple daily doses required with ENT. In this study, a higher proportion of patients on OPC vs ENT showed minimally, much, or very much improved Clinician (73% vs 50.9% respectively, p=0.0070) and Patient (72.1% vs 52.5% respectively, p=0.0091) Global Impression of Change scores.

A post hoc analysis of patient diary data showed that at the end of the DB study, for OPC 50mg, the proportion of patients who woke up in “On” status increased by 12.2% from baseline, in comparison with 7.5% for ENT. For OPC 50mg-treated patients, time to “On” decreased by 17.7% vs 1.9% for ENT. The reduction of morning “Off” time (%/h) was two-fold greater for OPC 50mg vs ENT (20% vs 10%), and no early morning “Off” (EMO) was observed for OPC 50mg (EMO was still observed for ENT).

The sub analysis of the OLE study showed that after one year, patients who switched from ENT to OPC and ended the OLE study on OPC 50mg had significant reductions in “Off” time (LS mean change: -68.2min; p=0.0025) and significant improvements in “On” time (LS mean change: +53.3min; p=0.0195).

Conclusion: Compared to ENT, OPC provides numerically higher reduction of “Off” time, increased “On” time, and a higher proportion of patients reporting meaningful clinical improvement. The benefit was maintained in the OLE study, further supporting its long-term efficacy. These findings suggest that OPC’s once-daily dosing offers an effective and convenient option for optimizing LD therapy in patients with PD.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/comparative-efficacy-of-opicapone-and-entacapone-in-the-management-of-motor-fluctuations-in-parkinsons-disease/