OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Opicapone – Ongentys®

DRUG CLASS

Parkinson Disease Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Opicapone	923287-50-7	C15-H10-Cl2-N4-O6

ANNOTATED BIBLIOGRAPHY

References updated: 25 October 2021

Abbreviations used: COMT, catechol O-methyltransferase; CPK, creatine phosphokinase; MAO, monoamine oxidase.

• Roberson ED. Parkinson Disease. Treatment of central nervous system degenerative disorders. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 328-333.

  (Textbook of pharmacology and therapeutics; COMT inhibitors are discussed).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2020/212489Orig1s000MedR.pdf.

  (FDA website, including product label and clinical review of data submitted in support of approval of opicapone, mentions that therapy is associated with a minimal rate of ALT elevations which was comparable to that of placebo [<1%], that elevations above 3 times ULN were rare, and there were no cases with concurrent bilirubin elevations).
• Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P. Bi-Park 1 investigators. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15:154–165. [PubMed: 26725544]

  (Among 600 adults with Parkinson disease with motor fluctuations while on levodopa who were treated with opicapone [5, 25, or 50 mg], entacapone [200 mg], or placebo once daily for 14-15 weeks, “off” time decreased by 60 minutes in the 50 mg dose group in comparison to placebo, which was non-inferior to entacapone, and total adverse event rates were similar in the three groups [54% vs 57% and 50%], dyskinesia was more frequent with opicapone [16% vs 8% and 4%] and “changes in laboratory tests…differed by <2% across visits for any treatment groups”).
• Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, Soares-da-Silva P., BIPARK-2 Study Investigators. Opicapone as adjunct to levodopa therapy in patients With Parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74:197–206. [PubMed: 28027332]

  (Among 427 adults with Parkinson disease and motor fluctuations while on levodopa treated with opicapone [25 or 50 mg] vs placebo for 14-15 weeks and then in an open phase with opicapone for one year, “off” time decreased 102 to 118 minutes with opicapone vs 65 minutes with placebo, and effects were maintained for the full year, while total adverse event rates were 71% vs 64%, dyskinesia rates 24% vs 8% and “no relevant liver function finding occurred in either phase”).
• Lees A, Ferreira JJ, Rocha JF, Rascol O, Poewe W, Gama H, Soares-da-Silva P. Safety profile of opicapone in the management of Parkinson's disease. J Parkinsons Dis. 2019;9:733–740. [PubMed: 31498127]

  (Analysis of pooled results of controlled trials and open label studies of opicapone as an adjunct for Parkinson disease [1614 patients] identified total adverse event rates for opicapone [25 and 50 mg daily combined] vs placebo to be 63.5% vs 57.5%, serious adverse events 3.5% vs 4.3%, dyskinesia 18.3% vs 6.2%, constipation 5.7% vs 1.9%, insomnia 5.1% vs 1.6%, CPK elevations 3.9% vs 1.9%, dizziness 3.7% vs 1.2%, somnolence 2.9% vs 1.9%, hallucinations 1.8% vs 0.4%, and that there were no relevant changes in liver enzymes and no serious hepatic adverse events).
• Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P. Long-term efficacy of opicapone in fluctuating Parkinson's disease patients: a pooled analysis of data from two phase 3 clinical trials and their open-label extensions. Eur J Neurol. 2019;26:953–960. [PMC free article: PMC6593852] [PubMed: 30681754]

  (Pooled results of two placebo-controlled trials of opicapone in adults with Parkinson disease and motor complications yielded an overall average decrease in “off” time compared to placebo of -35 minutes for the 25 mg dose and -58 minutes for the 50 mg dose with an accompanying increase in “on” time without worsening of dyskinesia; no information provided on safety results).
• Reichmann H, Lees A, Rocha JF, Magalhães D, Soares-da-Silva P., OPTIPARK investigators. Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020;9:9. [PMC free article: PMC7055125] [PubMed: 32345378]

  (Among 495 adults with Parkinson disease and motor fluctuations on levodopa therapy who were treated in an open label trial of opicapone [50 mg daily] in Germany for 3 months and the UK for 6 months, subjective improvement was reported in 71-85% of patients while the overall adverse event rate was 75%, serious adverse event rate 6.9%, and discontinuation rate for treatment relate adverse events 13%; no mention of ALT elevations or serious hepatic adverse events).
• Scott LJ. Opicapone: a review in Parkinson's disease. CNS Drugs. 2021;35:121–131. [PubMed: 33428178]

  (Review of the mechanism of action, pharmacology, clinical efficacy and tolerance of opicapone, the third COMT inhibitor approved in the US [having been approved in Europe in 2016], specifically comments that in clinical trials, it has no clinically relevant hepatobiliary adverse events).
• Opicapone (Ongentys) - a COMT inhibitor for Parkinson's disease. Med Lett Drugs Ther. 2021;63(1615):3–5. [PubMed: 33646998]

  (Concise review of mechanism of action, clinical efficacy, safety and costs of opicapone shortly after its approval for use in Parkinson disease, mentions adverse events of dyskinesia, constipation, creatine phosphokinase [CPK] elevations, hypotension, syncope, weight loss, drowsiness, hallucinations, delusions, agitation and withdrawal symptoms; mentions specifically that it has not been associated with hepatotoxicity).
• Drugs for Parkinson's disease. Med Lett Drugs Ther. 2021;63(1618):25–32. [PubMed: 33647001]

  (Concise review of current medications approved for use in Parkinson disease including levodopa/carbidopa, dopamine agonists, COMT inhibitors, monoamine oxidase [MAO]-B inhibitors, anticholinergics, and istradefylline, mentions hepatotoxicity of tolcapone but not of opicapone or any other of the adjunctive therapies).