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S18 Ivacaftor treatment in preschool children with cystic fibrosis and a CFTR gating mutation: extended evaluation
  1. JC Davies1,
  2. S Cunningham2,
  3. KW Southern3,
  4. S Robertson4,
  5. Y Green5,
  6. J Cooke5,
  7. M Higgins5,
  8. M Rosenfeld6
  1. 1Imperial College & Royal Brompton & Harefield NHS Foundation Trust, London, UK
  2. 2Royal Hospital for Sick Children, Edinburgh, UK
  3. 3Alder Hey Children’s Hospital, Liverpool, UK
  4. 4Vertex Pharmaceuticals Incorporated, Boston, USA
  5. 5Vertex Pharmaceuticals (Europe) Limited, Milton Park, UK
  6. 6Seattle Children’s Hospital, Seattle, USA

Abstract

Introduction and objectives Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has demonstrated improved outcomes in patients aged ≥6 years with cystic fibrosis (CF) and a CFTR gating mutation. The phase 3, open-label, 24-week KIWI study assessed safety and pharmacokinetics of ivacaftor (50- or 75-mg granules twice daily [bid] for weight.

Methods Patients who completed KIWI could enrol in KLIMB (an 84-week, open-label extension study). Dosing was the same as in KIWI for patients aged <6 years; for patients aged ≥6 years, dosing was 150-mg tablets bid.

Results KIWI enrolled 34 patients (mean age, 3.2 years); 33 enrolled in KLIMB. Cough was the most common AE in both KIWI (56%) and KLIMB (64%). Over the total 72-week treatment period, 8 patients had ALT or AST elevations of >8× the upper limit of normal (ULN), 6 of whom had liver function tests (LFTs) >2× ULN at pretreatment baseline. Six of the 8 patients with LFTs >8× ULN had drug interruption; study drug was subsequently resumed. In total, 3 patients permanently discontinued study drug (elevated LFTs, n = 2; needle phobia, n = 1). Improvements in sweat chloride, faecal elastase-1, and immunoreactive trypsinogen were maintained over 72 weeks. Overall improvements from baseline in other exploratory outcome measures were also observed (Table 1).

Abstract S18 Table 1

Summary of exploratory efficacy outcome measures

Conclusions A favourable overall safety profile was demonstrated with ivacaftor during extended follow-up in preschool patients with CF. Reported adverse events were consistent with the known safety profile of ivacaftor; additional monitoring of liver function may be required in this age group, particularly in patients with a history of elevated LFTs. Improvements in markers of pancreatic function and sweat chloride were sustained over the extended follow-up.

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