Ravulizumab Medicine 13 December 2018 Extended indication Treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) in patients with haemolysis with clinical symptom(s) indicative of high disease activity and in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months. Therapeutic value Possible equal value Total cost € 22,800,000.00 Registration phase Positive CHMP opinion Product Active substance Ravulizumab Domain Cardiovascular diseases Reason of inclusion New medicine (specialité) Main indication Other non-oncological hematological medications Extended indication Treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) in patients with haemolysis with clinical symptom(s) indicative of high disease activity and in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months. Current proprietary name Already available biosimilars / generics Proprietary name Ultomiris Manufacturer Alexion Portfolio holder Mechanism of action Complement inhibitor Route of administration Intravenous Therapeutical formulation Intravenous drip Budgetting framework Intermural (MSZ) Centre of expertise Radboud Nijmegen, AMC en Maastricht UMC Additional remarks Monoclonaal antilichaam gericht tegen het C5 complement eiwit. Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date June 2018 Expected Registration June 2019 Orphan drug Yes Registration phase Positive CHMP opinion Reimbursement Medicine sluice Additional remarks Positieve CHMP-opinie april 2019. Therapeutic value Current treatment options Eculizumab, allogene stamceltransplantatie Therapeutic value Possible equal value This assessment does not indicate any potential inclusion in the package. Substantiation Ravulizumab toont non-inferiority in fase III studies ten opzichte van eculizumab. Langere halfwaardetijd dan bestaande middelen, mogelijke meerwaarde in minder frequente toediening (1 maal per acht weken in plaats van 1 maal per twee weken). Gelijke effectiviteit verwacht met huidige behandeloptie. Duration of treatment Frequency of administration 1 times every 8 weeks Dosage per administration 2.400-3.600 mg References AA&PNH contactgroep; Richtlijn Paroxysmale Nachtelijke Hemoglobinurie; NCT03056040, fabrikant Kulasekararaj et al. Blood 2019;133(6):540-549 Lee et al. Blood 2018 :blood-2018-09-876136 Additional remarks Dosering afhankelijk van lichaamsgewicht: ≥ 40 to < 60 kg: 2.400 mg loading dose, 3.000 mg maintenance dose; ≥ 60 to < 100 kg: 2.700 mg loading dose, 3.300 mg maintenance dose; ≥ 100 kg, 3.000 mg loading dose, 3.600 mg maintenance dose. Expected patient volume per year Patient volume 40 - 80 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Fabrikant; AA&PNH contactgroep; GIPdatabank Additional remarks PNH wordt jaarlijks bij 40-80 mensen vastgesteld in Nederland. In 2015 gebruikten 85 patiënten eculizumab voor meerdere indicaties. Fabrikant: 120 (gediagnosticeerde populatie niet gelijk aan behandelde populatie [~70]), verwachting marktaandeel: 70% van de huidig behandelde populatie na drie jaar. Expected cost per patient per year Cost € 360,000.00 - 400,000.00 This amount gives an indication of the total cost. It is the result of the average expected patient volume times the average cost per patient. both per year. References Fabrikant; Farmatec Additional remarks De huidige kosten voor eculizumab bij de indicatie PNH zijn ongeveer €340.000 - €400.000 per patiënt per jaar. Dit is gebaseerd op de 78 flacons en de huidige lijstprijs. Aangezien ravulizumab zal moeten concurreren met eculizumab zal de prijs in dezelfde range vallen. Er komen echter biosimilars voor eculizumab, dus dat speelt waarschijnlijk belangrijke rol bij introductie ravulizumab. Potential total cost per year Total cost € 22,800,000.00 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