Dapagliflozine

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
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.
Proprietary name	Symkevi
Manufacturer	Vertex
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
Submission date	December 2019
Expected Registration	November 2020
Orphan drug	Yes
Registration phase	Registered and reimbursed
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
Substantiation	Aangezien CF een progressieve ziekte betreft, heeft behandeling op jonge leeftijd extra meerwaarde gezien schade dan (gedeeltelijk) voorkomen kan worden.
Duration of treatment	lifetime
Frequency of administration	2 times a day

Expected patient volume per year

Patient volume	< 107 Market share is generally not included unless otherwise stated.
References	Data CF registratie 2019
Additional remarks	Er komen in deze leeftijdsgroep maximaal 107 patiënten in aanmerking voor behandeling.

Patient volume

< 107

Market share is generally not included unless otherwise stated.

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
References	Fabrikant

Potential total cost per year

Total cost	19,795,000.00 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.

Total cost

19,795,000.00

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.

Off label use

Off label use	No
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"

Indication extension

Indication extension	Yes
Indication extensions	age extensions: - patients 2-5 yrs - patients 1-2 yrs - patients <1 years of age
References	Fabrikant

Other information

There is currently no futher information available.

Tezacaftor / ivacaftor