GVS assessment of ivacaftor/tezacaftor (Symkevi®) in combination with ivacaftor (Kalydeco®) for the treatment of cystic fibrosis

The National Health Care Institute completed its assessment whether an extension is possible of the conditions of List 2 of the GVS (Medicines Reimbursement System) for the use of the combination preparation tezacaftor 100 mg/ivacaftor 150 mg (Symkevi®) in a combination schedule with ivacaftor 150 mg (Kalydeco®) monopreparation. These medicines are used for the treatment of patients with cystic fibrosis. The National Health Care Institute does not advise to extend the further conditions.

Tezacaftor/ivacaftor (Symkevi®) and ivacaftor (Kalydeco®)

Symkevi® is a combination tablet. Each film-coated tablet contains 100 mg tezacaftor and 150 mg ivacaftor. Tezacaftor/ivacaftor (Symkevi®) is indicated in a combination schedule with ivacaftor (Kalydeco®) 150 mg tablets for the treatment of patients aged 12 years and older with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene or who are heterozygous for the F508del mutation and have specific mutations in the CFTR gene. 

The National Health Care Institute has previously issued advice, which you can read on this page: 

Tezacaftor/ivacaftor (Symkevi®) with ivacaftor monopreparation (Kalydeco®) for the treatment of cystic fibrosis

The National Health Care Institute's advice

The National Health Care Institute has concluded that tezacaftor/ivacaftor in combination with ivacaftor monopreparation has a therapeutic added value compared to standard symptomatic treatment. However, there are uncertainties about the effects after 104 weeks. The costs of tezacaftor/ivacaftor in combination with ivacaftor monopreparation per patient are high, resulting in a high budget impact. Therefore the estimated cost-effectiveness is very unfavourable. 

The National Health Care Institute does not advise to extend the further conditions set out in List 2 of the GVS unless a number of conditions are met by the occupational group on the one hand and the marketing authorisation holder on the other:

  • A very substantial price reduction for tezacaftor/ivacaftor in combination with ivacaftor monopreparation, given the great uncertainty about the treatment effectiveness in terms of survival and quality of life, as well as the high budget impact and unfavourable cost-effectiveness. 
  • Appropriate use criteria for the efficient application of the treatment. The National Health Care Institute is already in discussion with the occupational group about making arrangements for appropriate use. 
  • Tracking and recording long-term data by the occupational group to evaluate the effectiveness and safety of tezacaftor/ivacaftor in combination with ivacaftor monopreparation.

The National Health Care Institute advises the minister to enter into a European cooperation for (price) negotiations, to determine appropriate use and to evaluate medicinal products for the treatment of cystic fibrosis, also known as CFTR modulators.

List 2 conditions

If the application of Symkevi® in combination with Kalydeco® is included in the package after a successful price negotiation, we recommend the following expansion of the reimbursement conditions:

  • Condition for tezacaftor/ivacaftor combination preparation (Symkevi®): Only in combination with ivacaftor (Kalydeco®) for the treatment of cystic fibrosis (CF) patients aged 12 years and older who are heterozygous for the F508del mutation in the CFTR gene and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G or  3849+10kbC→T.
  • Condition for ivacaftor (Kalydeco®): Only in combination with tezacaftor/ivacaftor (Symkevi®) for the treatment of cystic fibrosis (CF) patients aged 12 years and older who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G or 3849+10kbC→T.

    This report is a summary of recommendations by the National Health Care Institute. The original text is in Dutch.