Cystic fibrosis: lumacaftor and ivacaftor appear safe in preschoolers

  • McNamara JJ & al.
  • Lancet Respir Med
  • 24/01/2019

  • Jenny Blair, MD
  • Clinical Essentials
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Takeaway

  • Among children ages 2-5 years with cystic fibrosis (CF) who are homozygous for F508del-CFTR mutation, lumacaftor and ivacaftor appear safe and well-tolerated.
  • Pancreatic biomarkers improved while on the therapy.
  • Extension study is ongoing. 

Why this matters

  • These CF transmembrane conductance regulator (CFTR) protein modulators have not previously been studied in children this young.

Key results

  • Drug and metabolite plasma concentrations were within expected ranges.
  • Mean changes, 24 weeks vs baseline: 
    • Sweat chloride: −31.7 (95% CI, −35.7 to −27.6) mmol/L.
    • Fecal elastase concentration: 52.6 (95% CI, 22.5-82.7) μg/g; 3 children achieved normal range.
    • Serum immunoreactive trypsinogen (IRT): −130.2 (95% CI, −192.3 to −68.1) ng/mL.
  • No new safety signals.

Study design

  • Phase 3, open-label, 2-part, multicenter study of children ages 2-5 years with confirmed CF caused by homozygous F508del-CFTR mutation.
  • Participants received weight-based doses of lumacaftor and ivacaftor every 12 hours, participating in either:
    • Part A: pharmacokinetics and safety study, 15 days (n=12); or
    • Part B: pharmacodynamics, efficacy, pharmacokinetics, and safety study, 24 weeks (n=60).
  • Outcomes: pharmacokinetics and safety.
  • Funding: Vertex Pharmaceuticals Incorporated.

Limitations

  • Very small study without a control group.