Tezacaftor / ivacaftor Medicine 13 December 2018 Extended indication Symkevi is indicated in a combination regimen with ivacaftor 150mg tablets for the treatment of patients with cystic fibrosis (CF) aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272‑26A→G, and 3849+10kbC→T. Therapeutic value Possible added value Total cost € 19,795,000.00 Registration phase Registered and reimbursed Product Active substance Tezacaftor / ivacaftor Domain Lung diseases Reason of inclusion Indication extension IND Main indication Cystic fibrosis Extended indication Symkevi is indicated in a combination regimen with ivacaftor 150mg tablets for the treatment of patients with cystic fibrosis (CF) aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272‑26A→G, and 3849+10kbC→T. Current proprietary name Already available biosimilars / generics Proprietary name Symkevi Manufacturer Vertex Portfolio holder Mechanism of action Protein chaperone Route of administration Oral Therapeutical formulation Tablet Budgetting framework Extramural (GVS) Centre of expertise UMCU, Haga Ziekenhuis, Erasmus MC, Amsterdam UMC, UMC St Radboud, UMCG, MUMC+ Additional remarks In patiënten met F508del mutatie. CFTR modulation. Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date December 2019 Expected Registration November 2020 Orphan drug Yes Registration phase Registered and reimbursed Reimbursement Medicine sluice Additional remarks Positieve CHMP-opinie in september 2020. Huidige bijlage 2 voorwaarde: uitsluitend in combinatie met ivacaftor voor de behandeling van cystische fibrose (CF) patiënten van 12 jaar en ouder die homozygoot zijn voor de F508del-mutatie in het CFTR-gen. Therapeutic value Current treatment options Geen vergelijkbare behandelopties bij deze leeftijdscategorie. Orkambi voor de homozygote F508del populatie. Therapeutic value Possible added value This assessment does not indicate any potential inclusion in the package. Substantiation Aangezien CF een progressieve ziekte betreft, heeft behandeling op jonge leeftijd extra meerwaarde gezien schade dan (gedeeltelijk) voorkomen kan worden. Duration of treatment Frequency of administration 2 times a day Dosage per administration References Additional remarks Expected patient volume per year Patient volume < 107 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Data CF registratie 2019 Additional remarks Er komen in deze leeftijdsgroep maximaal 107 patiënten in aanmerking voor behandeling. Expected cost per patient per year Cost € 185,000.00 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 Additional remarks Potential total cost per year Total cost € 19,795,000.00 Total cost for sluice Additional remarks Off label use Off label use No Indications off label use References Fabrikant: "Off label use risk to zero as product use and efficacy is related to CFTR mutation, for which NCFS registry data are exact estimate of prevalence" Additional remarks Indication extension Indication extensions Yes Indication extensions age extensions: - patients 2-5 yrs - patients 1-2 yrs - patients <1 years of age References Fabrikant Additional remarks Other information Additional remarks