Plozasiran Medicine 03 December 2024 Extended indication Familial chylomicronaemia syndrome in adults and elderly with elevated fasting triglycerides at screening refractory to standard lipid lowering therapy, monotherapy. Therapeutic value No estimate possible yet Total cost Registration phase Clinical trials Product Active substance Plozasiran Domain Metabolism and Endocrinology Reason of inclusion New medicine (specialité) Main indication Metabolic diseases Extended indication Familial chylomicronaemia syndrome in adults and elderly with elevated fasting triglycerides at screening refractory to standard lipid lowering therapy, monotherapy. Current proprietary name Already available biosimilars / generics Proprietary name ARO-APOC3 Manufacturer Arrowhead Portfolio holder Mechanism of action Other, see general comments Route of administration Subcutaneous Therapeutical formulation Injection Budgetting framework Extramural (GVS) Centre of expertise Additional remarks Apo C-III-remmer Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP No Submission date June 2025 Expected Registration March 2026 Orphan drug Yes Registration phase Clinical trials Reimbursement Medicine sluice Additional remarks Indieningsdatum en verwachte registratie op basis van IHSI-inschatting. Therapeutic value Current treatment options Volanesorsen Therapeutic value No estimate possible yet This assessment does not indicate any potential inclusion in the package. Substantiation Van de Apo C-III-remmers is volanesorsen geregistreerd als behandeling voor familiale chylomicronemie-syndroom en is olezarsen in ontwikkeling. De angiopoietin-like protein 3 remmers vupanorsen, evinacumab en zodasiran zijn ook in ontwikkeling. De effectiviteit van plozasiran lijkt gelijk aan volanesorsen; in de SHASTA-2 studie werd een 57 tot 77% reductie in triglyceriden aangetoond. Plozasiran heeft hoogstwaarschijnlijk niet de bijwerking thrombocytopenie (1,3). Duration of treatment Frequency of administration 1 times every 12 weeks Dosage per administration References Spagnuolo & Hegele. Exp. Rev. Endocrin. & Metab. 2024 (1); NCT05089084 (PALISADE) (2); Gaudet et al. JAMA Cardio. 2024 (3). Additional remarks Expected patient volume per year Patient volume 18 - 180 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Orphanet. 2024 (1). Additional remarks Familiale chylomicronemie-syndroom (FCS) heeft een geschatte prevalentie van 1 op 100.000 en 1 op 1.000.000 (1). Expected cost per patient per year Cost References Additional remarks Er is nog niets bekend over de mogelijke kosten. 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 Yes Indication extensions Mixed dyslipidaemia (1); Severe hypertriglyceridaemia (2-5). References NCT04998201 (MUIR) (1); NCT04720534 (SHASTA-2) (2); NCT06347003 (SHASTA-3) (3); NCT06347016 (SHASTA-4) (4); NCT06347133 (MUIR-3) (5). Additional remarks Plozasiran zit in fase 2 voor mixed dyslipidaemia (1) en in fase 3-trials voor severe hypertriglyceridaemia (2-5). Op basis van een primary completion datum in juli 2026 wordt de severe hypertrigliceridaemia uitbreiding eind 2027 verwacht. De mixed dyslipidaemia uitbreiding wordt later verwacht. Other information Additional remarks