Neurocrine Biosciences announced data analysis from two phase 3 trials evaluating opicapone added to levodopa for Parkinson’s disease was presented at an oral session at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. The analysis included data from more than 900 patients in the double-blind, placebo-controlled Phase III BIPARK-1 and BIPARK-2 studies. The study found that treatment with opicapone 50 mg, added to levodopa, resulted in a significant and sustained increase in ON time without troublesome dyskinesia, in Parkinson’s disease patients with motor fluctuations.
BIPARK-1 was a Phase III, randomized, double-blind placebo- and active-controlled study of opicapone as an adjunct to levodopa therapy in which approximately 600 patients with Parkinson’s disease and motor fluctuations received once-daily doses of opicapone (5 mg, 25 mg, or 50 mg), placebo or 200 mg of the COMT inhibitor entacapone for 14 to 15 weeks.
BIPARK-2 was a Phase III, randomized, double-blind placebo-controlled study of opicapone as an adjunct to levodopa therapy in which approximately 400 patients with Parkinson’s disease and motor fluctuations received once-daily doses of opicapone (25 mg or 50 mg) or placebo for 14 to 15 weeks.
The data presentation highlighted statistically significant increases in absolute ON time without troublesome dyskinesia from baseline (± standard error, hours) to the week 14/15 endpoint in both the BIPARK-1 (1.9±0.2 hours; for opicapone 50 mg vs. 0.9±0.2 hours for placebo) and BIPARK-2 (1.7±0.3 hours for opicapone 50 mg vs. 0.9±0.3 hours for placebo) studies. The improvements in ON time without troublesome dyskinesia were sustained in all patients treated with opicapone (all doses) in the one-year long-term open-label extension studies, with an average increase from baseline (± standard error, hours) of 2.0±2.6 hours in BIPARK-1 (n=494) and 1.8±3.2 hours for BIPARK-2 (n=339). In addition, a significantly higher percentage of patients treated with opicapone 50 mg had an increase in total ON time of an hour or longer at week 14/15 in both BIPARK-1 (65.2%) and BIPARK-2 (61.9%).
Pooled safety data from the double-blind opicapone-treated population (n=631) showed that 17.4% patients treated with opicapone (all doses) reported dyskinesia as a treatment-emergent adverse event (TEAE) versus 6.2% in placebo-treated patients. Only 1.9% of opicapone-treated patients discontinued treatment due to dyskinesia and only 0.3% experienced dyskinesia as a serious TEAE. Other adverse events included constipation, insomnia and dry mouth.
About Parkinson’s disease
Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disorder that affects approximately one million people in the U.S and six million people worldwide. Parkinson’s disease is characterized by a loss of dopamine and its function. Dopamine is a chemical “messenger” that is produced in the brain and is involved in the control of movement. As Parkinson’s progresses, dopamine production steadily decreases resulting in slowed movement (bradykinesia), tremor, rigidity, impaired posture and balance, and speech and writing difficulty.
There is no present cure for Parkinson’s disease and management consists of controlling the motor symptoms primarily through administration of dopaminergic therapies, including levodopa. While levodopa improves the control of Parkinson’s motor symptoms, the disease progresses, and the beneficial effects of levodopa begin to wear off, symptoms worsen and patients experience motor fluctuations.
Opicapone is a novel, once-daily, peripherally-acting, selective catechol-O-methyltransferase (COMT) inhibitor. Opicapone works by prolonging the duration of effect of levodopa through decreasing its conversion rate into 3-O-methyldopa, thereby reducing the OFF time and extending the ON time period associated with Parkinson’s treatment.
Neurocrine Biosciences in-licensed opicapone from BIAL in February 2017 and has exclusive development and commercialization rights in the U.S. and Canada.
The European Commission approved Ongentys (opicapone) in June of 2016 as an adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors (DDCIs) in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilized on those combinations.