Opicapone for the treatment of Parkinson's disease: A review of a new licensed medicine

Abstract

A BS TRACT: Catechol-O-methyl transferase inhibitors are currently used as first-line add-on therapy to levodopa for the treatment of end-of-dose motor fluctuations in Parkinson's disease patients, as they increase levodopa bioavailability. Several factors hamper the use of current available catechol-O-methyl transferase inhibitors, that is, the moderate efficacy and multiple dosing for entacapone and the risk of liver toxicity with tolcapone. Opicapone, a new long-acting, peripherally selective, once-daily catechol-O-methyl transferase inhibitor, was recently licensed in Europe. Two phase 3 doubleblind clinical trials demonstrated opicapone efficacy in reducing OFF time by an average of about 60 minutes daily compared with placebo, without increasing ON time with troublesome dyskinesias. These effects were also maintained during a subsequent open-label extension consisting of 1-year follow-up. Opicapone showed a good safety profile. From June 2016, Opicapone received the approval for marketing authorization from the European Commission as adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in patients with PD and end-of-dose motor fluctuations. We aimed to review the clinical pharmacological data of opicapone, summarize its clinical efficacy and safety issues, and discuss its potential role in the management of Parkinson's disease.Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. 1 Levodopa (L-dopa) continues to be the most efficacious therapeutic drug for PD treatment. 2 Nevertheless, long-term treatment with L-dopa leads to troublesome motor fluctuations or L-dopa-induced dyskinesia (LID). 3,4 The control of motor fluctuations is a key clinical need for almost all PD patients. 4 Up to 50% of patients can develop mild motor fluctuations within 2 years of initiating L-dopa therapy, 5 and this percentage increases to 70% after 9 years of sustained therapy, 6 with substantial effect on patients' quality of life. 7 End-of-dose motor fluctuations are linked to the short half-life of oral L-dopa (about 60-90 minutes). 8 Catechol-O-methyl transferase (COMT) inhibitors are currently used as add-on therapy to L-dopa for the amelioration of end-of-dose motor fluctuations, as they inhibit peripheral L-dopa metabolism and increase the delivery of L-dopa to the brain. 9 Opicapone (OPC), a new COMT ---

Opicapone for the treatment of Parkinson’s disease: an update

“…Currently two COMT inhibitors are in regular use: ENT and TLC [7]. ENT is a safe product to be given several times a day [10].…”

“…• Further comparative studies and broader trial inclusion criteria are needed to help the decision between COMT inhibitors and to expand the patient spectrum where this drug can be applied. Currently OPC is in phase 4 trial (OPTIPARK, European Union) to examine the safety and tolerability of a 50 mg OPC dose in a selected PD population [7]. Currently OPC is marketed under the Ongentys® brand name in the United Kingdom, Germany, Spain, Italy and North America [7,10].…”

“…From a chemical perspective, OPC is a peripherally acting compound, which has very high protein-binding affinity (in the subpicomolar range) to the COMT enzyme [7,16]. The pyridine N-oxide residue (position 3) is responsible for this inhibitory potential and cell toxicity avoidance [17].…”

“…Interestingly, despite the relatively short half-life time, the COMT inhibitory effect of OPC can be detected even after 24 hours, due to the slow dissociation rate [18]. Therefore, a once-daily dosing regimen is sufficient [7,10].…”

“…The gold standard of symptomatic therapy is levodopa (L-dopa; LD) [6]. The most prominent debilitating complication of long-lasting LD treatment is the development of motor complications [7]. Two years after the start of substitution therapy, around 50% of patients sense some degree of fluctuation in motor performance [8].…”