Zilucoplan Medicine 07 June 2022 Extended indication Generalized Myasthenia Gravis Therapeutic value No estimate possible yet Total cost Registration phase Registration application pending Product Active substance Zilucoplan Domain Neurological disorders Reason of inclusion New medicine (specialité) Main indication Neurological disorders other Extended indication Generalized Myasthenia Gravis Current proprietary name Already available biosimilars / generics Proprietary name Manufacturer UCB Portfolio holder UCB Mechanism of action Unknown Route of administration Subcutaneous Therapeutical formulation Injection Budgetting framework Extramural (GVS) Centre of expertise LUMC / MUCM+ / AUMC (loc. AMC) Additional remarks Mechanism of Action: zilucoplan is a synthetic macrocyclic peptide inhibitor of the terminal complement protein C5, with potential anti-inflammatory and cell protective activities. Upon subcutaneous administration, complement inhibitor zilucoplan binds to a unique site in terminal complement protein C5, which blocks C5 cleavage into C5a and C5b and prevents the C5b-dependent assembly of the membrane-attack complex (MAC). Zilucoplan also inhibits the interaction between C5b and C6, thereby further blocking MAC assembly. Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date 2022 Expected Registration 2023 Orphan drug Unknown Registration phase Registration application pending Reimbursement Medicine sluice Additional remarks submission date expected late second half of 2022 Therapeutic value Current treatment options Cholinesterase inhibitors, corticosteroids, Immunosuppressants, Intravenous, Immunoglobulins, bloodplasma transfer, Rituximab, Eculizumab Therapeutic value No estimate possible yet This assessment does not indicate any potential inclusion in the package. Substantiation Fase 2 studie afgerond. In vergelijking met placebo laat het geneesmiddel positieve resultaten zien (1). Een fase 3 studie zou verder uitsluitsel moeten geven over de therapeutische waarde van dit geneesmiddel ten opzichte van andere beschikbare geneesmiddelen (2). Op basis van de beschikbare data wordt op dit moment verwacht dat de nieuwe complementremmers ongeveer gelijk zullen presteren aan eculizumab. Duration of treatment Frequency of administration 1 times a day Dosage per administration tbd References Howard JF Jr, Nowak RJ, Wolfe GI, et al. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial. JAMA Neurol. 2020;77(5):582-592. doi:10.1001/jamaneurol.2019.5125, (NCT03315130, fase 2) (1), Studie-opzet fase 3-studie (NCT04115293) (2); NCT03971422) Additional remarks Expected patient volume per year Patient volume < 1,530 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Bol P. Myasthenia gravis. Ned Tijdschr Tandheelkd. 2001; 108:416-7 Additional remarks De prevalentie van myasthenia gravis ligt wereldwijd tussen de 5 en 20 op de 100.000 inwoners (1). In Nederland is de prevalentie geschat op 8 tot 9 op de 100.000 (1). In NL zou dit neerkomen op 1360-1530 (uitgaande van 17 miljoen inwoners). Het product zal moeten concurreren met andere middelen in de pijplijn voor deze indicatie. Het is op dit moment nog niet mogelijk een inschatting te doen welk middel welke plaats in de behandeling krijgt. Expected cost per patient per year Cost References Additional remarks Potential total cost per year Total cost Total cost for sluice Additional remarks Off label use Off label use Unknown Indications off label use References Additional remarks Indication extension Indication extensions Unknown Indication extensions References Additional remarks Other information Additional remarks