The preclinical discovery and development of opicapone for the treatment of Parkinson’s disease

References

• Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3(1):17013.
   PubMed Web of Science ®Google Scholar
• Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020;27:27–42.
   PubMed Web of Science ®Google Scholar
• Baizabal-Carvallo JF, Hallett M, Jankovic J. Pathogenesis and pathophysiology of functional (psychogenic) movement disorders. Neurobiol Dis. 2019;127:32–44.
   PubMed Web of Science ®Google Scholar
• Simon DK, Tanner CM, Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med. 2020 Feb;36(1):1–12.
   PubMed Web of Science ®Google Scholar
• Cheong SL, Federico S, Spalluto G, et al. The current status of pharmacotherapy for the treatment of Parkinson’s disease: transition from single-target to multitarget therapy. Drug Discov Today. 2019;24(9):1769–1783.
   PubMed Web of Science ®Google Scholar
• Zesiewicz TA. Parkinson Disease. Continuum (Minneap Minn). 2019;25:896–918.
   PubMedGoogle Scholar
• Lang A, Lees A. Management of Parkinson’s disease: an evidence based review. Mov Disord. 2002;17(Suppl 4):S1–166.
   PubMed Web of Science ®Google Scholar
• Gupta HV, Lyons KE, Pahwa R. Old drugs, new delivery systems in Parkinson’s disease. Drugs Aging. 2019;36(9):807–821.
   PubMed Web of Science ®Google Scholar
• Barroso SDS, Lopes LES, Santos KS, et al. Technological prospection: patents mapping involving compounds for the treatment of L-DOPA-induced dyskinesias. Expert Opin Ther Pat. 2019;29(12):979–985.
   PubMed Web of Science ®Google Scholar
• Marino BLB, Souza LR, Sousa KPA, et al. Parkinson’s disease: a review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment. Mini Rev Med Chem. 2019 Nov 3;19. DOI:10.2174/1389557519666191104110908
   Web of Science ®Google Scholar
• Factor SA, Burkhard PR, Caroff S, et al. Recent developments in drug-induced movement disorders: a mixed picture. Lancet Neurol. 2019;18(9):880–890.
   PubMed Web of Science ®Google Scholar
• Hoy SM. Levodopa/Carbidopa Enteral suspension: a review in advanced Parkinson’s disease. Drugs. 2019;79(15):1709–1718.
   PubMed Web of Science ®Google Scholar
• Rascol O, Perez-Lloret S, Ferreira JJ. New treatments for levodopa-induced motor complications. Mov Disord. 2015;30(11):1451–1460.
   PubMed Web of Science ®Google Scholar
• Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev. 2004;4:CD004554.
   Google Scholar
• Männistö PT, Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 1999;51(4):593–628.
   PubMed Web of Science ®Google Scholar
• Bonifácio MJ, Palma PN, Almeida L, et al. Catechol-O-methyltransferase and its inhibitors in Parkinson’s disease. CNS Drug Rev. 2007;13(3):352–379.
   PubMedGoogle Scholar
• Kiss LE, Soares-da-Silva P. Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility. J Med Chem. 2014;57:8692–8717.
   PubMed Web of Science ®Google Scholar
• Learmonth DA, Kiss LE, Soares-da-Silva P. The chemistry of catechol-O-methyltransferase inhibitors. Int Rev Neurobiol. 2010;95:119–162.
   PubMed Web of Science ®Google Scholar
• Kiss LE, Ferreira HS, Torrão L, et al. Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2010;53:3396–3411.
   PubMed Web of Science ®Google Scholar
• Entacapone. LiverTox: clinical and research information on drug-induced liver injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–2017 Jul 20.
   Google Scholar
• Tolcapone. LiverTox: clinical and research information on drug-induced liver injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–2017 Jul 20.
   Google Scholar
• Brooks DJ. Safety and tolerability of COMT inhibitors. Neurology. 2004;62(1 Suppl 1):S39–46.
   PubMed Web of Science ®Google Scholar
• EMA. Ongentys. Assessment Report. EMA/343011/2016. Avaliable from http://www.ema.europa.eu/ema/Index.jsp?curl=pages/medicines/human/medicines/002790/humanmed001950.jsp&mid=WC0b01ac058001d124
   Google Scholar
• Palma N, Bonifacio MJ, Loureiro AI, et al. Computation of binding affinity of catechol-o-methyltransferase-opicapone complexes. Parkinsonism Rel Disord. 2012;18S2:S81–S159.
   Google Scholar
• 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.
   Google Scholar
• Axelrod J, Laroche MJ. Inhibitor of O-methylation of epinephrine and norepinephrine in vitro and in vivo. Science. 1959;130(3378):800.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Ongentys (opicapone): EPAR - public assessment report. 2016b [cited 2016 Oct 20]. Available from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002790/WC500209538.pdf
   Google Scholar
• Bonifácio MJ, Torrão L, Loureiro AI, et al. Pharmacological profile of opicapone, a third-generation nitrocatechol catechol-Omethyl transferase inhibitor, in the rat. Br J Pharmacol. 2015;172:1739–1752.
   PubMed Web of Science ®Google Scholar
• Bonifácio MJ, Torrao MF, Loureiro A, et al. Pharmacological profile of Opicapone in Wistar rat. Catecholamine Research in the 21st Century. 2014, 83.
   Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. A single- and multiple-dose study to investigate the pharmacokinetics and pharmacodynamics of opicapone, a novel COMT inhibitor, in rat. Neuropharmacology. 2017;125:146–155.
   PubMed Web of Science ®Google Scholar
• Bonifácio MJ, Sutcliffe JS, Torrão L, et al. Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. Neuropharmacology. 2014;77:334–341.
   PubMed Web of Science ®Google Scholar
• Kitajima T, Mizote S, Bonifácio MJ, et al. Inhibition of catechol-O-methyltransferase in the cynomolgus monkey by opicapone after acute and repeated administration. Neuropharmacology. 2018;143:282–288.
   PubMed Web of Science ®Google Scholar
• Kitajima T, Bonifácio M, Moser P, et al. Novel COMT inhibitor opicapone shows sustained inhibition and improved L-DOPA availability in monkeys. International Congress of Parkinson’s Disease and Movement Disorders® October 5–9, 2018; Hong Kong, 345.
   Google Scholar
• Bonifácio MJ, Sousa F, Soares-da-Silva P. Opicapone improves the effects of l-dopa on the mptp-induced parkinson’s-like syndrome in cynomolgus monkeys. J Neurol Sci. 2017;381(Suppl 15):217–218.
   Web of Science ®Google Scholar
• Bonifacio MJ, Sousa F, Medakkar S, et al. Opicapone improved the effect of L-DOPA on the MPTP induced Parkinson’s-like syndrome in cynomolgus monkeys. Parkinsonism Rel Disord. 2016;22:e149ee192.
   Google Scholar
• Moura E, Bonifacio MJ, Soares-da-Silva P. Opicapone improves the levodopa induced rotational behavior in 6-OHDA hemiparkinsonian rats. Parkinsonism Rel Disord. 2016;22:e149ee192.
   Google Scholar
• Loureiro AI, Fernandes-Lopes C, Soares-da-Silva P. Distribution, metabolism and elimination of opicapone in the rat and non-human primates. Parkinsonism Rel Disord. 2016;22:e149ee192.
   Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat. Toxicol Appl Pharmacol. 2017;323:9–15.
   PubMed Web of Science ®Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. Development of a liquid chromatography assay for the determination of opicapone and BIA 9-1079 in rat matrices. Biomed Chromatogr. 2016;30(3):312–322.
   PubMed Web of Science ®Google Scholar
• Bonifacio MJ, Sutcliffe JS, Torrao LS. Brain and peripheral levodopa pharmacokinetics in the cynomolgus monkey following administration of opicapone, a novel catechol-o-methyltransferase inhibitor. Parkinsonism Rel Disord. 2012;18S2:S81–S159.
   Google Scholar
• Bonifácio MJ, Sutcliffe JS, Torrão L, et al. Effect of Opicapone, a new Catechol-O-Methyltransferase inhibitor, in levodopa pharmakokinetics in the cynomolgous monkey. Catecholamine Research in the 21st Century, 2014, 79.
   Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. Pharmacokinetics of opicapone, a novel catecholomethyltransferase inhibitor, in the wistar rat. Parkinsonism Rel Disord. 2016;22:e149ee192.
   Google Scholar
• Loureiro AI, Fernandes-Lopes C, Soares-da-Silva P. Distribution, metabolism and elimination of opicapone in the rat and non-human primates. Parkinsonism Relat Disord. 2016;22(Supplement 2):e184.
   Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. Pharmacokinetics of opicapone, a novel catechol-O-methyltransferase inhibitor, in the Wistar rat. Parkinsonism Relat Disord. 2016;22(Supplement 2):e184.
   Google Scholar
• Gonçalves D, Alves G, Fortuna A, et al. An HPLC-DAD method for the simultaneous quantification of opicapone (BIA 9-1067) and its active metabolite in human plasma. Analyst. 2013;138(8):2463–2469.
   PubMed Web of Science ®Google Scholar
• Rocha JF, Falcão A, Santos A, et al. Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations. Eur J Clin Pharmacol. 2014;70(9):1059–1071.
   PubMed Web of Science ®Google Scholar
• Rocha JF, Sicard É, Fauchoux N, et al. Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics. Br J Clin Pharmacol. 2017;83(3):540–553.
   PubMed Web of Science ®Google Scholar
• Rocha JF, Almeida L, Falcão A, et al. Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects. Br J Clin Pharmacol. 2013;76(5):763–775.
   PubMed Web of Science ®Google Scholar
• Almeida L, Rocha JF, Falcão A, et al. Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013;52(2):139–151.
   PubMed Web of Science ®Google Scholar
• Bonifácio MJ, Sousa F, Soares-da-Silva P. Potential drug toxicity of nitrocatechol COMT inhibitors in HepaRG. Toxicol Lett. 2015;238(2):S319.
   Web of Science ®Google Scholar
• Lopes N, Ferreira J, Lees A, et al. Hepatic safety of opicapone in Parkinson’s disease patients. Mov Disord. 2015;30(Suppl 1):263.
   Google Scholar
• Lees A, Ferreira JJ, Rocha JF, et al. Safety profile of Opicapone in the management of Parkinson’s disease. J Parkinsons Dis. 2019;9(4):733–740.
   PubMedGoogle Scholar
• Costa R, Oliveira C, Pinto R, et al. One-year open-label efficacy and safety of opicapone in Parkinson’s disease BIPARK-II study. Mov Disord. 2014;29(Suppl 1):630.
   Google Scholar
• Pinto R, Vaz-da-Silva M, Lopes N, et al. Cardiac safety of opicapone in patients with Parkinson’s disease: analysis of the centralized phase III ECG dataset. Mov Disord. 2015;30(Suppl 1):294.
   Google Scholar
• Pinto R, l’Hostis P, Patat A, et al. Evaluation of opicapone on cardiac repolarization in a thorough QT/QTc study. Clin Pharmacol Drug Dev. 2015;4(6):454–462.
   PubMed Web of Science ®Google Scholar
• Castro Caldas A, Teodoro T, Ferreira JJ. The launch of opicapone for Parkinson’s disease: negatives versus positives. Expert Opin Drug Saf. 2018;17(3):331–337.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Lees A, Rocha JF, et al. 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(2):154–165.
   PubMed Web of Science ®Google Scholar
• Lees AJ, Ferreira J, Rascol O, et al. 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(2):197–206.
   PubMed Web of Science ®Google Scholar
• Lopes N, Ferreira J, Lees A, et al. Exploratory efficacy of opicapone in fluctuating Parkinson’s disease patients at different stages of symptom progression. Mov Disord. 2016;31(suppl 2):S642.
   PubMedGoogle Scholar
• Lees A, Ferreira J, Lopes N, et al. Efficacy and safety of opicapone in patients over 70 years with Parkinson’s disease and motor fluctuations. Mov Disord. 2015;30(suppl 1):S99.
   Google Scholar
• Ferreira J, Lees A, Rocha J, et al. Efficacy and safety of opicapone in patients with Parkinson’s disease and motor fluctuations: 1-year follow-up (bipark I). J Neurol Sci. 2015;357:e255–e294.
   Web of Science ®Google Scholar
• Ferreira JJ, Rocha JF, Falcão A, et al. Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics, motor response, and erythrocyte-COMT activity in Parkinson’s patients co-administered with levodopa/dopa-decarboxylase inhibitor. J Neurol Sci. 2013;333(Suppl 1):e116.
   Google Scholar
• Lees A, Ferreira JJ, Costa R, et al. Efficacy and safety of opicapone, a new COMT-inhibitor, for the treatment of motor fluctuations in Parkinson’s Disease patients: BIPARK-II studyA. J Neurol Sci. 2013;333(Suppl 1):e116.
   Google Scholar
• Rocha JF, Falcão AR, Pinto R, et al. Effect of opicapone and entacapone on levodopa pharmacokinetics when administered with immediate release 100/25 mg levodopa/carbidopa in healthy subjects. J Neurol Sci. 2013;333(Suppl 1):e115.
   Google Scholar
• Bonifacio MJ, Torrao LS, Loureiro AI, et al. Opicapone: characterization of a novel peripheral long-acting catechol-o-methyltransferase inhibidor. Parkinsonism Rel Disord. 2012;18S2:S81–S159.
   Google Scholar
• Ferreira JJ, Lees A, Rocha J, et al. Efficacy and safety of opicapone in patients with Parkinson’s disease and motor fluctuations: 1- year follow-up (Bipark I). J Neurol Sci. 2015;357:e285.
   PubMed Web of Science ®Google Scholar
• Lees AJ, Ferreira J, Rascol O, et al. Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson’s disease treated with L-DOPA. Expert Rev Neurother. 2017;17(7):649–659.
   PubMed Web of Science ®Google Scholar
• Fabbri M, Ferreira JJ, Lees A, et al. Opicapone for the treatment of Parkinson’s disease: A review of a new licensed medicine. Mov Disord. 2018;33(10):1528–1539.
   PubMed Web of Science ®Google Scholar
• Ferreira J, Lees A, Tolosa E, et al. Switching double-blind opicapone, entacapone or placebo to open-label opicapone: efficacy results of the 1-year extension of study BIPARK I. Mov Disord. 2016;31(suppl 2):S633.
   Google Scholar
• Ferreira J, Lees A, Rascol O, et al. Activities of daily living and motor scores of the UPDRS in fluctuating Parkinson’s disease treated with opicapone. Mov Disord. 2016;31(suppl 2):S643.
   Google Scholar
• Costa R, Oliveira C, Pinto R, et al. One-year open-label efficacy and safety of opicapone in Parkinson’s disease BIPARK-II study. Mov Disord. 2014;29(suppl 1):S233.
   Google Scholar
• Ferreira J, Lees A, Lopes N, et al. Pooled efficacy of opicapone as adjunctive therapy to levodopa in patients with Parkinson’s disease and motor fluctuations. Parkinsonism Rel Disord. 2016;22:e87ee141.
   Google Scholar
• Lees A, Ferreira J, Gama H, et al. Pooled safety and tolerability of opicapone in the treatment of Parkinson’s disease and motor fluctuations. Parkinsonism Rel Disord. 2016;22:e87ee141.
   Google Scholar
• Ferreira JJ, Lees A, Rocha JF, et al. 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(7):953–960.
   PubMed Web of Science ®Google Scholar
• GlobalData (2014). Parkinson’s disease – current and future players, March 2014, GDHC1033FPR.
   Google Scholar
• GlobalData (2014). Opicapone (Parkinson’s disease) – forecast and market analysis to 2022, March 2014, GDHC402DFR.
   Google Scholar
• Ferreira JJ, Lees AJ, Poewe W, et al. Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease. Neurology. 2018;90(21):e1849–e1857.
   PubMed Web of Science ®Google Scholar
• Bet L, Bareggi SR, Pacei F, et al. Bimodal administration of entacapone in Parkinson’s disease patients improves motor control. Eur J Neurol. 2008;15(3):268–273.
   PubMed Web of Science ®Google Scholar
• Kaakkola S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson’s disease. Int Rev Neurobiol. 2010;95:207–225.
   PubMed Web of Science ®Google Scholar
• Gordin A, Kaakkola S, Teräväinen H. Clinical advantages of COMT inhibition with entacapone - a review. J Neural Transm (Vienna). 2004;111(10–11):1343–1363.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Katzenschlager R, Bloem BR, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol. 2013;20:5–15.
   PubMed Web of Science ®Google Scholar
• The Parkinson Study Group QE3 Investigators. A randomized clinical trial of high dosage Coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543–552.
   PubMed Web of Science ®Google Scholar
• Jankovic J, Goodman I, Safirstein B, et al. Safety and tolerability of Multiple ascending doses of PRX002/RG7935, an anti-α-Synuclein monoclonal antibody, in patients with parkinson disease: a randomized clinical trial. JAMA Neurol. 2018;75(10):1206–1214.
   PubMed Web of Science ®Google Scholar
• Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211–218.
   PubMed Web of Science ®Google Scholar
• Marks WJ Jr, Baumann TL, Bartus RT. Long-term safety of patients with Parkinson’s disease receiving rAAV2-Neurturin (CERE-120) gene transfer. Hum Gene Ther. 2016;27(7):522–527.
   PubMed Web of Science ®Google Scholar
• Bartus RT, Baumann TL, Siffert J, et al. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology. 2013;80(18):1698–1701.
   PubMed Web of Science ®Google Scholar
• Blits B, Petry H. Perspective on the road toward gene therapy for Parkinson’s disease. Front Neuroanat. 2017;10:128.
   PubMed Web of Science ®Google Scholar
• Whone A, Luz M, Boca M, et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain. 2019;142(3):512–525.
   PubMed Web of Science ®Google Scholar
• Whone AL, Boca M, Luz M, et al. Extended treatment with glial cell line-derived neurotrophic factor in Parkinson’s disease. J Parkinsons Dis. 2019;9(2):301–313.
   PubMedGoogle Scholar