Valsartan / sacubitril Medicine 09 January 2018 Extended indication Entresto is indicated in adult patients for treatment of symptomatic chronic heart failure with ejection fraction below 55/60% Therapeutic value No judgement Total cost € 5,400,000.00 Registration phase Clinical trials Product Active substance Valsartan / sacubitril Domain Cardiovascular diseases Reason of inclusion Indication extension IND Main indication Other medication for cardiovascular diseases Extended indication Entresto is indicated in adult patients for treatment of symptomatic chronic heart failure with ejection fraction below 55/60% Current proprietary name Already available biosimilars / generics Proprietary name Entresto Manufacturer Novartis Portfolio holder Mechanism of action Combination therapy Route of administration Oral Therapeutical formulation Tablet Budgetting framework Extramural (GVS) Centre of expertise Additional remarks Angiotensinereceptor-neprilysine-remmer (ARNI). Entresto vertoont het werkingsmechanisme van een angiotensinereceptor-neprilysine-remmer door tegelijk neprilysine (neutrale endopeptidase, NEP) te remmen via LBQ657, de werkzame metaboliet van de prodrug sacubitril, en door de angiotensine II type 1-receptor (AT1-receptor) te blokkeren via valsartan. De aanvullende cardiovasculaire voordelen van Entresto bij patiënten met hartfalen worden toegeschreven aan de versterking van de peptiden die worden afgebroken door neprilysine, zoals natriuretische peptiden (NP), door LBQ657 en de gelijktijdige remming van de effecten van angiotensine II door valsartan. Registration Registration route Centralised (EMA) Type of trajectory Unknown Particularity Unknown ATMP Unknown Submission date December 2019 Expected Registration November 2020 Orphan drug No Registration phase Clinical trials Reimbursement Medicine sluice Additional remarks Entresto is momenteel beschikbaar voor de behandeling van volwassen patiënten met symptomatisch chronisch hartfalen met verminderde ejectiefractie. Therapeutic value Current treatment options Geen evidence-based behandeling. Therapeutic value No judgement This assessment does not indicate any potential inclusion in the package. Substantiation Er zijn nog geen resultaten van de PARAGON trial Duration of treatment Frequency of administration 2 times a day Dosage per administration 103 mg / 97 mg References PARAGON -HF studie (NCT01920711); Solomon et al. JACC: Heart Failure, 5(7), 471-482. ; Solomon et al. Circulation: Heart Failure, 11(7), e004962. Additional remarks Expected patient volume per year Patient volume < 3,000 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Expertopinie; GIPdatabank Additional remarks De verwachting is dat er minder patiënten hiervoor in aanmerking komen dan bij de huidige indicatie van Entresto het geval is. Er waren 2.754 gebruikers van Entresto in 2017, inschatting: minder dan 3.000 gebruikers per jaar. Expected cost per patient per year Cost € 1,800.00 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 medicijnkosten.nl Additional remarks Kost €2,50 per tablet. Voor behandeling op jaarbasis zo'n €1.800. Potential total cost per year Total cost € 5,400,000.00 Total cost for sluice Additional remarks Off label use Off label use No Indications off label use References Additional remarks Indication extension Indication extensions Yes Indication extensions Verwachte indiening Post-acute myocardial infarction: 2020 References novartis pipeline Additional remarks Other information Additional remarks