The prescription drug user fee act target date is scheduled for April 26, 2020.
Eiry Roberts, MD
The FDA has accepted a new drug application for opicapone, a novel, once-daily, oral, selective catechol-O-methyltransferase (COMT) inhibitor as an adjunctive treatment to levodopa/carbidopa for Parkinson disease OFF episodes, announced Neurocrine Biosciences.
The new drug application is backed by data from 38 clinical studies, including 2 phase 3 studies (BIPARK-1 and BIPARK-2), with more than 1000 patients treated with opicapone. The FDA has set a prescription drug user fee act target action date of April 26, 2020.
“People living with Parkinson disease often struggle to control their motor fluctuations due to the progressive neurodegenerative effects of the disorder,” Eiry Roberts, MD, chief medical officer, Neurocrine Biosciences, said in a statement.1
“With opicapone, we aim to prolong the benefits of levodopa by providing a new treatment option to patients with Parkinson disease in the United States. It is our goal to help patients maintain good ON time — the period when their motor symptoms are better controlled — and reduce OFF time — the period when the effects of levodopa have worn off. We look forward to working with the FDA to bring this new treatment option to patients coping with this debilitating disorder.”
BIPARK-1, a phase 3, double-blind, placebo- and active-controlled study, evaluated the safety and efficacy of opicapone in approximately 600 patients with Parkinson disease and motor fluctuations. Participants were randomized to receive once-daily opicapone in 5 mg (n=119), 25 mg (n=116), or 50 mg (n=115) doses compared to entacapone 200 mg (n=120) and placebo (n=120) for 14 to 15 weeks. The trial revealed a placebo-adjusted OFF time reduction for the 50-mg group of 60.8 minutes, a 51% greater decrease than the 40.3-minute reduction observed in the entacapone-treated group.2
In data from a 1-year, open-label extension
from the BIPARK 1 trial, opicapone not only maintained its efficacy over 1 year but also resulted in 65-minute (P
<.0001) and 39-minute (P
= .0060) decreases in mean off time for patients who switched from placebo (n=81) and entacapone (n=87), respectively. On time without dyskinesia also increased for those patients by 43 minutes (P
= .0247) and 46 minutes (P
= .0148), respectively.3
The second, phase 3, randomized, double-blind, placebo-controlled study, BIPARK-2, assessed opicapone as an adjunct to levodopa therapy in approximately 400 patients with Parkinson disease and motor fluctuations. Study participants received once-daily opicapone 25 mg or 50 mg or placebo for 14 to 15 weeks. There was a 54.3-minute reduction in off-time versus placebo for the 50-mg/day dose of opicapone. After 1 year of treatment, daily off-time was reduced by 126.3 minutes with opicapone.4
In both studies, the primary endpoint was the change from baseline in absolute time in the OFF state, assessed by patient diaries.
Opicapone works by prolonging the clinical effect of levodopa by decreasing its conversion rate into 3-O-methyldopa to allow for greater availability in the brain.
The European Commission approved opicapone in June 2016 as an adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors in adults with Parkinson and end-of-dose motor fluctuations who cannot be stabilized on those combinations.
1. Neurocrine Biosciences Announces FDA Acceptance of New Drug Application for Opicapone as an Adjunctive Treatment for Patients with Parkinson's Disease [news release]. San Diego: Neurocrine Biosciences; July 10, 2019. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-fda-acceptance-of-new-drug-application-for-opicapone-as-an-adjunctive-treatment-for-patients-with-parkinsons-disease-300882953.html. Accessed July 10, 2019.
2. Ferreira J, Lees A, Rocha J-F, et al. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: arandomised, double-blind, controlled trial. 2016; 15(2): 154-165. doi: 10.1016/S1474-4422(15)00336-1.
3. Ferreira J, Lees A, Tolosa E, et al. Switch of Double-Blind Opicapone, Entacapone, or Placebo to Open-Label Opicapone: Efficacy Results of the 1-year Extension of StudyBIPARK I. Presented at: IAPRD; Lyon, France; August 19-22. Accessed July 10, 2019.
4. Lees AJ, Ferreira JJ, Rascol O, et al. Opicapone asadjunct to levodopa therapy in patients with Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):197-206.