Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a G551D Mutation

Abstract

Rationale: Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. Objectives: This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele. Methods: Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n ¼ 26) or placebo (n ¼ 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies. Measurements and Main Results: Despite near-normal mean baseline values in FEV 1 , patients receiving ivacaftor had a significant increase in percent predicted FEV 1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P , 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P , 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was 253.5 mmol/L (P , 0.001) versus placebo. The incidence of adverse events was similar in the two groups. Conclusions: In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).

Genetic, cell biological, and clinical interrogation of theCFTR mutation c.3700 A>G (p.Ile1234Val) informs strategies for future medical intervention

“…VX-770 (or Ivacaftor) has been approved in North America and Europe as a drug for patients bearing the relatively rare mutation: p.Gly551Asp. 7,8 The p.Gly551Asp mutation causes defective channel gating, [9][10][11] and VX-770 is thought to be effective in partially restoring lung function in patients with p.Gly551Asp because it enhances the channel activity of this mutant. [12][13][14][15] The most common mutation in Europe and North America, p.Phe508del, has been studied extensively and has been found to impair CFTR protein folding during synthesis.…”

Clinical care for primary ciliary dyskinesia: current challenges and future directions

“…In CF, early results from studies investigating the use of small-molecule compounds that target the underlying defect have been encouraging [97][98][99]. However, RCTs in gene therapy for CF have so far failed to demonstrate clinical effectiveness [100].…”

Novosti v Obravnavi Pljučne Bolezni Pri Otrocih in Mladostnikih S Cistično Fibrozo

“…Tudi pri tej skupini je ivacaftor pokazal pomemben porast FEV 1 (12,5 %) in porast telesne teže za 2,8 kg glede na placebo. 42 Raziskovalci menijo, da je prihodnost zdravljenja v t. i. personalizirani medicini, ko bo zdravljenje usmerjeno glede na specifično motnjo oz. gensko okvaro.43…”