KALYDECO (ivacaftor) - Cystic fibrosis (CF) in patients aged 2 years and older

The clinical benefit of KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with KALYDECO (ivacaftor) remains substantial in the MA indication.

Considering:

• initial evidence of the efficacy of KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with KALYDECO (ivacaftor) in phase 3 studies in patients with at least one F508del mutation, which had demonstrated a substantial size effect versus placebo (when no medicinal product was available in the mutation concerned) or clinically relevant comparators, on clinically relevant endpoints, with, in particular, robust assessment of the improvement in quality of life, in the short term, with a maximum study duration of 24 weeks,
• the results of the seven open-label extension studies conducted following the initial clinical studies, concerning 1,266 patients, with follow-up of up to 192 weeks, suggesting maintenance of the clinical benefit observed in the initial studies for lung function, CFTR function measured by sweat chloride concentration, nutritional parameters, and reduction in the number of pulmonary
  exacerbations,
• the results of the post-registration study based on the cystic fibrosis registry, which was of excellent quality and met the Committee’s expectations for real-world data to assess the impact of triple therapy on morbidity and mortality in real-world practice, in particular showing a reduction in the number of hospitalisations, healthcare utilisation, particularly the use of antibiotics, recourse to enteral nutrition, and a sharp fall in the number of lung transplants and deaths,
• the safety profile of triple therapy, which appears to be favourable, characterised by an elevation in transaminases, with attention drawn to behavioural disturbances,
• immediate and long-lasting effects of triple therapy with, in particular, a sharp fall in mortality due to the disease and the radical transformation of its management, previously poorly controlled,

the Committee deems that KAFTRIO 37.5 mg/25 mg/50 mg, 75 mg/50 mg/100 mg (ivacaftor/tezacaftor/elexacaftor) film-coated tablets, 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 tablets, and KALYDECO 59.5 mg, 75 mg (ivacaftor) granules in sachet provide a major clinical added value (CAV I) in the current care pathway, which includes the relevant comparators (see paragraph).