GVS advice elexacaftor/tezacaftor/ivacaftor (Kaftrio®) in combination with ivacaftor (Kalydeco®): extension of further conditions

The National Health Care Institute has completed its assessment whether the further conditions of elexacaftor/tezacaftor/ivacaftor (Kaftrio®) in combination with ivacaftor (Kalydeco®) could be extended. The application for the extension of the further conditions is related to patients aged 6 to 11 with cystic fibrosis having at least one F508del mutation in the CFTR gene. The National Health Care Institute advises the Minister to amend the further conditions for elexacaftor/tezacaftor/ivacaftor and ivacaftor mono preparation as below and extend them with the assessed indication. 

Indication for which reimbursement is requested

Since 1 January 2022, elexacaftor/tezacaftor/ivacaftor (Kaftrio®) has been included in the Medicine Reimbursement System (GVS) on List 1B, subject to further reimbursement conditions.

The current further conditions for elexacaftor/tezacaftor/ivacaftor are:
Only in combination with ivacaftor for the treatment of cystic fibrosis (CF) patients aged 12 years and older who have at least one F508del mutation in the CFTR gene. 

Since 1 June 2015, ivacaftor (Kalydeco®) has been included in the medicine reimbursement system (GVS) on List 1B, subject to further reimbursement conditions.

The current further conditions for ivacaftor are as follows.

Only for cystic fibrosis (CF) patients:

  1. with the ’gating mutations’ for which ivacaftor is registered, 
  2. with an R117H mutation for which ivacaftor is registered, 
  3. six years and older in combination with tezacaftor/ivacaftor who 
    a    are homozygotic for the F508del mutation in the CFTR gene, 
    b    are heterozygotic for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A-G, 5945L, 5977F, R1070W, D1152H, 2789+5G–A, 3272-26A-1G and 3849+10kbC-, T, or
  4. twelve years and older who have at least one F508del mutation in the CFTR gene, in combination with elexacaftor/tezacaftor/ivacaftor. 

In November 2021, the European Medicines Agency (EMA) approved the extension of the existing indication of elexacaftor/tezacaftor/ivacaftor with ivacaftor to include the use for CF patients aged 6 to 11 who have at least one F508del mutation in the CFTR gene. This indication is now subject to a request for reimbursement.

National Health Care Institute's advice

The National Health Care Institute advises the Minister to amend the further conditions for elexacaftor/tezacaftor/ivacaftor and ivacaftor mono preparation as below and extend them with the assessed indication. 

The National Health Care Institute also recommends that the combination therapy be regularly evaluated based on the start and stop criteria established by the physicians' association. During previous assessments of CFTR modulators, agreements were already reached about this; this assessment will be taken into account.

Adjustment of further conditions for elexacaftor/tezacaftor/ivacaftor (Kaftrio®) 

Only in combination with ivacaftor for the treatment of cystic fibrosis (CF) patients aged 6 years and older who have at least one F508del mutation in the CFTR gene. 

Adjustment of further condition for ivacaftor (Kalydeco®)

Only in combination with elexacaftor/tezacaftor/ivacaftor for the treatment of cystic fibrosis (CF) patients aged 6 years and older who have at least one F508del mutation in the CFTR gene. 

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