In the 1-year open-label extension of the EPSILON trial, adding opicapone to levodopa in non-fluctuating Parkinson's patients produced sustained improvement in motor scores and a non-significant trend toward fewer motor complications (80.2% vs 69.7%, p=0.1).

Findings support early adjunctive COMT inhibition as a safe, translatable symptomatic strategy that may delay motor complications, making it relevant for clinical management and pragmatic therapeutic optimization even though it does not demonstrate disease modification.

Primary results from the 24-week EPSILON study (NCT04978597) showed that adding opicapone to levodopa in non-fluctuating Parkinson's patients significantly improved motor impairment without increasing the development of motor complications versus placebo. All participants finishing the double-blind phase became eligible for open-label treatment with opicapone. Symptomatic efficacy of opicapone was maintained with 1-year open-label treatment (adjusted-mean ± SE change in MDS-UPDRS motor score from double-blind baseline to Week 76: -7.4 ± 0.81); participants who switched from placebo to opicapone had a motor improvement of -6.1 ± 0.79. At Week 76, 80.2% of opicapone-opicapone-treated participants remained motor complication-free versus 69.7% in the placebo-opicapone group (p = 0.1).