Clazosentan Medicine 07 June 2022 Extended indication Prevention of delayed cerebral ischaemia due to cerebral vasospasm associated with aneurysmal subarachnoid haemorrhage (SAH) Therapeutic value No estimate possible yet Total cost Registration phase Clinical trials Product Active substance Clazosentan Domain Neurological disorders Reason of inclusion New medicine (specialité) Main indication Neurological disorders other Extended indication Prevention of delayed cerebral ischaemia due to cerebral vasospasm associated with aneurysmal subarachnoid haemorrhage (SAH) Current proprietary name Already available biosimilars / generics Proprietary name Pivlaz Manufacturer Idorsia Pharmaceuticals Portfolio holder Mechanism of action Unknown Route of administration Intravenous Therapeutical formulation Injection / infusion solution Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Werkingsmechanisme: Endothelin A receptor antagonists. Endotheline is een langwerkende endogene vasocontrictor. Na SAH is de concentratie endotheline mogelijk verhoogd en is er verhoogde gevoeligheid. Een antagonist zou de vasospasmen reduceren. Vasospasmen kunnen in 17 tot 40% van de gevallen delayed ischemic neurological deficit (DIND) veroorzaken. De helft hiervan ontwikkelt een cerebraal infarct. Registration Registration route Centralised (EMA) Type of trajectory Unknown Particularity Unknown ATMP No Submission date 2024 Expected Registration 2025 Orphan drug Yes Registration phase Clinical trials Reimbursement Medicine sluice Additional remarks Middel is geregistreerd in Japan. Global studie (NCT03585270) heeft lichte vertraging opgelopen door COVID-pandemie Therapeutic value Current treatment options Therapeutic value No estimate possible yet This assessment does not indicate any potential inclusion in the package. Substantiation CONSCIOUS-1 trial en Japans/Koreaanse trial laten zien dat middel mogelijk van preventieve waarde kan zijn bij vaatspasmen voor dit indicatiegebied (1, 2), echter nog geen verbetering van de functionele uitkomst. Er loopt een fase 3 studie (3). Op basis van de huidige studies is nog onduidelijk of middel ook in de richtlijn opgenomen zal worden (4). Duration of treatment Maximal 14 day / days Frequency of administration Dosage per administration 15 mg/hour References Macdonald et al., (2008) Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008 Nov;39(11):3015-21 (1); Fujimura M, et al. Cerebrovasc Dis 2017;44:59–67 (fase 2, Japans/Koreaanse trial) (2); Studieprotocol fase 3-studie: NCT03585270 (3); Expert opinie (4) Additional remarks Expected patient volume per year Patient volume Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References doi: 10.1001/jamaneurol.2019.0006. Additional remarks De incidentie van SAH in Europa is in 2010 geschat op 6.3 (CI 4.9-8.1) per 100.000 per jaar. In Nederland zou dit neerkomen op 1.071 (CI: 816-1377) (op basis van 17 miljoen Nederlanders) patiënten. Hoeveel hiervan in aanmerking komt voor dit middels is momenteel niet te voorspellen. 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