Neurocrine Biosciences Presents Phase III Data Analysis Demonstrating that Opicapone Added to Levodopa Resulted in a Significant and Sustained Increase in ON Time without Troublesome Dyskinesia in Parkinson's Disease Patients with Motor Fluctuations
"The analysis of data from these two Phase III trials showed that adding once-daily opicapone to levodopa significantly increased ON time without troublesome dyskinesia, a common concern for patients with Parkinson's disease," said
Opicapone is in development in the U.S. for adjunctive use with levodopa for the treatment of Parkinson's disease. Levodopa is effective for treating motor symptoms, but troublesome side effects may develop with chronic use of levodopa and progression of disease. These side effects include involuntary movements (dyskinesia) and fluctuations between "ON time," periods when the medication is working and Parkinson's disease symptoms are controlled, and "OFF time," when the medication isn't working and motor and non-motor symptoms return.
"Managing Parkinson's disease is complex and challenging because symptoms worsen as the disease progresses and first-line treatments such as levodopa begin to lose effectiveness over time, placing an increasing burden on patients and caregivers," said Eiry W. Roberts, M.D., Chief Medical Officer at
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; p=0.002 for opicapone 50 mg [n=107] vs. 0.9±0.2 hours for placebo [n=110]) and BIPARK-2 (1.7±0.3 hours; p=0.025 for opicapone 50 mg [n=124] vs. 0.9±0.3 hours for placebo [n=122]) 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%, n=115; p<0.01) and BIPARK-2 (61.9%, n=147; p<0.01).
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 (n=257). Only 1.9% of opicapone-treated patients discontinued treatment due to a TEAE of dyskinesia and only 0.3% experienced dyskinesia as a serious TEAE. Other TEAEs included constipation (5.2% and 1.9%), insomnia (4.4% and 1.6%) and dry mouth (4.1% and 1.2%) in opicapone- and placebo-treated patients, respectively.
BIPARK-1 and BIPARK-2 were conducted by BIAL –
About the BIPARK-1 Study
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. The primary endpoint was the change from baseline in absolute time in the OFF state, as assessed by patient diaries; the primary analysis followed a hierarchical procedure for each opicapone dose in which superiority compared with placebo in the full analysis set was first tested and then, if positive, non-inferiority to entacapone was tested in the per-protocol set with a margin of 30 minutes. The initial study period was followed by a one-year open-label phase during which all patients received treatment with opicapone. Primary outcomes from the BIPARK-1 study were previously published in Lancet Neurology, with the outcomes from the open-label extension phase of the BIPARK-1 study subsequently published in Neurology.
About the BIPARK-2 Study
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 primary endpoint was the change from baseline in absolute time in the OFF state, as assessed by patient diaries. The initial study period was followed by a one-year open-label phase during which all patients received treatment with opicapone. Primary outcomes from the BIPARK-2 study and the open-label extension were previously published in JAMA Neurology.
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, an investigational treatment for Parkinson's disease in the U.S., 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. Discovered by the BIAL laboratories, it is designed to provide patients and physicians with a once-daily option for the treatment of Parkinson's disease.
In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: the Company's future financial and operating performance; risks or uncertainties related to the development of the Company's product candidates, including opicapone; risks and uncertainties relating to competitive products and technological changes that may limit demand for opicapone; risks associated with the Company's dependence on BIAL for development and manufacturing activities related to opicapone, and the ability of the Company to manage BIAL; risks that the
1 Troublesome dyskinesia was defined as either no dyskinesia or non-troublesome dyskinesia
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Neurocrine Biosciences, Navjot Rai (Media & Investors), 858-617-7623, IR@neurocrine.com