KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with KALYDECO (ivacaftor) - Cystic fibrosis (CF) aged 2 to less than 6 years

The Committee deems that the clinical benefit of KAFTRIO 75 mg/50 mg/100 mg, 60 mg/40 mg/80 mg (ivacaftor/tezacaftor/elexacaftor) granules in sachets in a combination regimen with KALYDECO 59.5 mg, 75 mg (ivacaftor) granules in sachets is substantial in the MA indication.

Considering:

• the exploratory results of a phase 3 non-comparative trial and its extension, which aimed to assess the safety and pharmacokinetics of KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with KALYDECO (ivacaftor) in children aged 2 to less than 6 years who are homozygous for the F508del mutation, or heterozygous for the F508del mutation in the CFTR gene and who have a minimal function mutation in the CFTR gene, suggesting an efficacy on lung clearance index and sweat chloride level, a biological marker of CFTR function, however with limited follow-up,
• the acceptable safety profile in children aged 2 years to less than 6 years, which appears to be similar to that observed in older patients,
• the need to have access to effective, well-tolerated treatments in this age group,

and despite:

• results for episodes of acute respiratory exacerbation assessed following administration of triple therapy only but not prior to its administration,
• the heterogeneous and incomplete pancreatic efficacy data suggested by the evolution in faecal elastase,
• the heterogeneity of the sweat response observed between homozygous and heterozygous patients,
• the absence of results in terms of quality of life,
• the absence of comparative data in patients aged 2 to less than 6 years who are homozygous for the F508del mutation, or heterozygous for the F508del mutation in the CFTR gene and who have a gating mutation, indications for which there are clinically relevant comparators,
• the need for a safety assessment in this age group with longer follow-up,

the Committee deems that, as in patients aged 6 years and older, KAFTRIO 75 mg/50 mg/100 mg, 60 mg/40 mg/80 mg (ivacaftor/tezacaftor/elexacaftor) granules in sachets in a combination regimen with KALYDECO 59.5 mg, 75 mg (ivacaftor) granules in sachets provides:

• a substantial clinical added value (CAV II) in the care pathway for cystic fibrosis in paediatric patients aged 2 to less than 6 years who are homozygous for the F508del mutation in the CFTR gene, or heterozygous for the F508del mutation in the CFTR gene and who have a minimal function mutation in the CFTR

a minor clinical added value (CAV IV) in the care pathway for cystic fibrosis in paediatric patients aged 2 to less than 6 years who are heterozygous for the F508del mutation in the CFTR gene and who have a residual function mutation or a gating mutation.