KAFTRIO (ivacaftor/tezacaftor/elexacaftor) / KALYDECO (ivacaftor) - Cystic fibrosis patients aged 2 years and older

Opinions on drugs - Posted on Sep 18 2025

Reason for request

Modification of the listing conditions

Summary of opinion

Favourable opinion for reimbursement of “KAFTRIO (ivacaftor/tezacaftor/elexacaftor) is indicated in combination with KALYDECO (ivacaftor) in the treatment of cystic fibrosis patients aged 2 years and older, who are carriers of at least one non-class I mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene and who are not carriers of an F508del mutation of the CFTR gene”.

Clinical Benefit

Substantial

The clinical benefit of KAFTRIO 37.5 mg/25 mg/50 mg, 75 mg/50 mg/100 mg (ivacaftor/tezacaftor/elexacaftor) film-coated tablet, KAFTRIO 60 mg/40 mg/80 mg, 75 mg/50 mg/100 mg (ivacaftor/tezacaftor/elexacaftor) granules in sachet, in combination with KALYDECO 75 mg, 150 mg (ivacaftor) film-coated tablet, KALYDECO 59.5 mg, 75 mg (ivacaftor) granules in sachet, is substantial in the extension of the MA indication.

Clinical Added Value

important

Considering:

the evidence of the efficacy of KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in combination with KALYDECO (ivacaftor) in a phase III study involving patients aged 6 and older with rare non-F508del mutations, with the demonstration of a substantial effect size versus placebo on various clinically relevant criteria at 24 weeks, and interim results at 48 weeks from the extension study suggesting maintenance of efficacy;
the lack of comparison of the triple therapy with the clinically relevant comparator KALYDECO (ivacaftor) as monotherapy, indicated for only nine non-F508del mutations; triple therapy having already demonstrated clinical and biological benefit compared with ivacaftor alone in older patients who are heterozygous for the F508del mutation in the CFTR gene and carrying one of the regulatory defect mutations, such as a “gating” mutation;
the absence of clinical data in patients aged 2 to less than 6 years old with non-F508del mutations; the clinical data available in this age group, already assessed by the Committee, concerns patients with the F508del mutation of the CFTR gene and suggests efficacy on the lung clearance index and the concentration of sudoral chlorine, a biological marker of CFTR function, with limited follow-up;
the safety profile of triple therapy in patients without F508del mutations, which appears favourable and consistent with that seen in patients carrying F508del mutations;

the Committee considers that KAFTRIO 37.5 mg/25 mg/50 mg, 75 mg/50 mg/100 mg (ivacaftor/tezacaftor/elexacaftor) film-coated tablet, KAFTRIO 60 mg/40 mg/80 mg, 75 mg/50 mg/100 mg (ivacaftor/tezacaftor/elexacaftor) granules in sachet, in combination with KALYDECO 75 mg, 150 mg (ivacaftor) film-coated tablet, and KALYDECO 59.5 mg, 75 mg (ivacaftor) granules in sachet, provide substantial clinical added value (CAV II) in the current therapeutic strategy which includes the relevant comparator.

Avis économique

Le périmètre de l’avis économique retenu par la CEESP est restreint par rapport à la demande de remboursement aux patients NON-F/NON-GATING en raison de l’absence de données chez les patients NON-F/GATING et de l’exclusion de KALYDECO, comparateur pertinent dans la population NON-F/GATING, des comparateurs de l’analyse. La population de l’évaluation économique et de l’impact budgétaire représente environ 90% de la population de la demande de remboursement.

La Commission évaluation économique et de santé publique conclut que :

les RDCR présentés par l’industriel ne sont pas interprétables, qu’ils soient exprimés en coût/QALY, en raison de la réserve majeure portant sur l’estimation des scores d’utilité, ou en coût/AVG en raison de l’incertitude globale majeure générée notamment par les hypothèses fortes sur lesquelles reposent l’analyse ;

l’introduction de KAFTRIO en association à KALYDECO dans la population NON-F/NON-GATING entraine un impact budgétaire cumulé à 3 ans estimé à 376,3 millions d’euros.

> KAFTRIO / KALYDECO - Avis économique (pdf)