Opicapone Can Increase Length of ON-Periods in Patients With Parkinson Disease

Treatment with once-daily opicapone in addition to levodopa increased ON-time, without troublesome dyskinesia, in Parkinson disease (PD) patients who experienced fluctuations in motor symptoms, according to an abstract presented by Neurocrine Biosciences Inc at the 2019 American Academy of Neurology Annual Meeting that took place in Philadelphia, Pennsylvania, May 4-10.

Developed by BIAL and commercialized through an agreement with Neurocrine, opicapone is a peripherally-acting, highly selective, catechol-O-methyltransferase (COMT) inhibitor. The drug extends the duration of levodopa’s effects by decreasing its conversion rate into 3-O-methyldopa.

While levodopa, the long-term standard of care for PD, can effectively treat motor symptoms of PD, troublesome side effects can occur due to its chronic use and disease progression. These side effects include dyskinesia and fluctuations between “ON” periods, when motor and nonmotor symptoms are effectively controlled by medication, and "OFF" periods, when medication becomes ineffective and PD 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 Roberts, MD, chief medical officer at Neurocrine Biosciences, in a statement. "Based on the phase 3 data analysis, we believe once-daily opicapone has the potential to prolong the clinical effects of levodopa and help patients achieve symptom control so they can better cope with this debilitating disease."

BIA9-1067 in Idiopathic Parkinson's Disease Patients (BIPARK)-1 and -2 studies evaluated whether opicapone could extend the length of time PD patients experience “ON” periods. The trials included over 900 PD patients who struggled to control their motor symptoms. The studies were double-blind, randomized, and placebo-controlled. Participants received varying doses of opicapone, in addition to levodopa, for 14 to 15 weeks, or placebo. Participants may have also been given entacapone in BIPARK-1 but not in BIPARK-2. Participant who completed a double-blind study were invited to participate in a 1-year open-label phase of either study.

Data were combined for both studies and results for 50 mg doses were presented. The data presentation revealed statistically significant increases in absolute “ON” time without reports of dyskinesia from baseline to week 14 or 15 endpoints. All patients treated with opicapone in the open-label extension studies experienced improvements in “ON” time without dyskinesia. From baseline, the average increase in “ON” time was 2.0 ± 2.6 hours in BIPARK-1 and 1.8 ± 3.2 hours in BIPARK-2. Also, a significantly higher percentage of patients who received 50 mg doses of opicapone had an increase in total “ON” time of an hour or longer at week 14 or 15 in both BIPARK-1 and BIPARK-2.

"The analysis of data from these 2 phase 3 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 Peter LeWitt, MD, director of the Parkinson's Disease and Movement Disorders Program at the Henry Ford Hospital in Detroit, and the study’s lead researcher, in a statement. "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."

Neurocrine plans to submit a new drug application with FDA during this quarter.

NOTE: This article has been updated to correct the anticipated time frame for filing the NDA.

Reference

LeWitt P, Claassen D, Olson K, et al. Once-daily Opicapone increases ON-time in patients with Parkinson’s disease: results from two phase 3 studies. Presented at: 2019 American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. https://n.neurology.org/content/92/15_Supplement/S4.003. Neurology. 2019;92(suppl 15):S4.003.