Objective: To compare efficacy and safety outcomes with safinamide and opicapone as adjuncts to levodopa in Parkinson’s disease (PD) patients with wearing-off using an anchored matching-adjusted indirect comparison (MAIC).

Background: Safinamide and opicapone are effective adjunctive therapies for wearing‑off in PD. However, no head-to-head trial has directly compared their clinical effects.

Method: Anchored MAIC was conducted using individual patient data from the ME2125-3 study (safinamide 50 and 100 mg/day, 24 weeks) [1], and aggregated data from the COMFORT-PD study (opicapone 25 mg/day, 14-15 weeks; the approved dose in Japan) [2]. Eligible ME2125-3 patients partially met COMFORT‑PD severity criteria. Baseline variables adjusted for matching included age, sex, disease duration, daily OFF-time, daily levodopa dose, and BMI. Efficacy outcomes were the mean changes in daily OFF-time and UPDRS scores from baseline to endpoint. Safety outcomes include rates of adverse events (AEs) and adverse drugs reactions (ADRs). Adjusted safinamide–placebo effects were estimated via weighted ANCOVA, and indirect comparisons versus opicapone were computed using Bucher’s method based on published placebo‑adjusted effects.

Results: After matching, prespecified baseline patient characteristics were balanced between both trial populations. Safinamide 50 and 100 mg/day demonstrated numerically greater reduction in daily OFF-time compared with opicapone 25 mg/day (Mean difference with opicapone 25mg/day: -0.7 to -0.8 h), although these differences didn’t reach statistical significance (p=0.100 – 0.113). In contrast, safinamide showed significant greater improvement in UPDRS Part III scores (-3.0 for 50 mg/day, -4.0 for 100 mg/day; both p<0.01). Safinamide also showed benefit on UPDRS Part I scores relative to opicapone (-0.3 for 50 mg/day, p=0.040; -0.3 for 100 mg/day, p=0.114). There were no marked differences in AEs and ADRs.

Conclusion: Compared to opicapone 25 mg/day, safinamide as adjunct to levodopa provided greater improvement in motor symptoms and certain non-motor symptoms, while both produce comparable daily OFF-time reductions in PD patients. These findings suggest that safinamide may offer broader symptomatic benefits for Japanese PD patients experiencing wearing-off, although confirmatory head-to-head trials are warranted.

References: [1] Hattori N, Tsuboi Y, Yamamoto A, Sasagawa Y, Nomoto M; ME2125-3 Study Group. Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled, phase II/III study. Parkinsonism Relat Disord. 2020;75:17-23.
[2] Takeda A, Takahashi R, Tsuboi Y, et al. Randomized, Controlled Study of Opicapone in Japanese Parkinson’s Patients with Motor Fluctuations. Mov Disord. 2021;36(2):415-423.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparative-efficacy-and-safety-of-safinamide-versus-opicapone-in-japanese-patients-with-parkinsons-disease-and-wearing-off-a-matching-adjusted-indirect-comparison/