San Diego-based Neurocrine Biosciences presented data from two Phase III clinical trials of opicapone, a once-daily, oral catechol-O-methyltransferase (COMT) inhibitor for Parkinson’s disease. They found that patients receiving opicapone 50 mg with levodopa, the standard of care, had a significant and sustained improvement in symptoms.

Specifically, the studies found that the combination of the drugs had a significant and sustained increase in ON time without problematic dyskinesia in Parkinson’s patients who had motor fluctuations. Also, more than 60% of the patients receiving opicapone had greater than or equal to a one-hour improvement from baseline in total ON time at week 14/15.

Levodopa, as mentioned earlier, is the standard-of-care for Parkinson’s disease. However, for many patients, levodopa begins to wear off more quickly, which triggers what is called a medication “on-off phenomenon.” What this means is that if you take the drug on a regular basis, you won’t notice a difference in symptoms between doses. But once the on-off phenomenon begins, the ON period is when the drug seems to be working, but the OFF period is when it doesn’t work as well or at all. In these cases, the ON states become shorter and the OFF state occurs earlier.

Neurocrine reported on two Phase III studies, BIPARK-1 and BIPARK-2. BIPARK-1 looked at about 600 patients with Parkinson’s and motor fluctuations. They received once-daily doses of three separate doses of opicapone, 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. Both trials had one-year extension phases.

BIPARK-2 looked at about 400 patients with Parkinson’s and motor fluctuations. They received once-daily doses of opicapone of either 25 mg or 50 mg or placebo for 14 to 15 weeks. The primary endpoint change from baseline in absolute time in the OFF state.

“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,” stated Peter LeWitt, director of the Parkinson’s Disease and Movement Disorders Program at Henry Ford Hospital in Detroit. “We believe this data will translate into real-world benefits for Parkinson’s disease patients on levodopa therapy who experience motor fluctuations, which can be disruptive and impact the patient’s quality of life.”

The studies were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Results from BIPARK-1 were previously published in Lancet Neurology, with data from the extension phase published in Neurology. Primary outcomes from BIPARK-2 and the open-label extension were previously published in JAMA Neurology.

Opicapone was discovered by BIAL. The European Commission approved Ongentys (opicapone) in June 2016 as an adjunct therapy to levodopa/DOPA decarboxylase inhibitors (DDCIs) in adults with Parkinson’s disease and end-of-dose motor fluctuations who can’t be stabilized on those combinations. In February 2018, Neurocrine licensed opicapone for development and commercialization in the U.S. and Canada from BIAL.

“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,” stated Eiry W. Roberts, Neurocrine’s chief medical officer. “Based on the Phase III data analysis, we believe once-daily opicapone has the potential to prolong the clinical effects of levodopa and help patients achieve symptoms control so they can better cope with this debilitating disease.”



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