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The commentary on ivacaftor for patients homozygous for Phe508del-CFTR (c.1521_1523delCTT; formerly F508del) ‘Should we curb our enthusiasm?’ by Jones and Barry makes a number of important points regarding the potential impact of ivacaftor/lumacaftor combination in cystic fibrosis (CF).1 However, the view taken by the authors is rather pessimistic regarding the scientific and clinical impact of combination therapy for people with CF. The TRAFFIC and TRANSPORT studies were designed to test the efficacy and safety of this combination in line with regulatory requirements from the Federal Drugs Administration and European Medicines Agency (EMA). The phase III pivotal programme, as noted in the commentary, met its primary end point of improvement in FEV1, with significant changes in secondary end points in the pooled analyses of frequency of exacerbations and quality of life.2 The reduction in exacerbations (39%) and hospitalisations (61%) are clinically important outcomes as frequent exacerbations are associated with accelerated decline in lung function and worse survival.3 ,4 In a study recently published using registry data from patients with the Gly551Asp mutation treated with ivacaftor in the clinic, there is continued benefit in attenuation of the rate of decline in lung function.5 This suggests that the benefits of restoration of cystic fibrosis transmembrane conductance regulator (CFTR) function go beyond initial improvement in FEV1 alone.
The scientific underpinning of combination therapy is that lumacaftor has a correcting effect on mutant Phe508del-CFTR, increasing its …
Footnotes
Contributors All authors contributed to this letter.
Funding The authors received institutional funding to undertake clinical trials with Vertex products.
Competing interests JSE reports receiving payment for consultancy and serving on advisory boards from Novartis and Vertex, Celtaxsys and Aptalis., lecture fees from Vertex and Gilead Sciences. All payments were made to Queen's University Belfast. The following have provided institutional payments to undertale clinical trials, Vertex, Novartis, Celtaxsys, Aptalis and ProQR. CW reports receiving consulting fees from Medscape and Vertex, lecture fees and travel support from Vertex and Novartis, grant support from Vertex, GlaxoSmithKline and Novo Nordisk, and fees on a per patient basis as principal investigator of a clinical study from Boehringer Ingelheim. BR reports receiving grant support from Achaogen, Apartia, Bayer Healthcare, Breathe Easy, Bristol-Myers Squibb, Catabasis, 12th Man Technologies, Caltaxsys, Corbus Pharmaceuticals, Cornerstone Therapeutics, CSL Behring, CURx Pharmaceuticals, Eli Lilly, Flatley Discovery Lab, Genentech, Gilead Sciences, GlycoMimetics, Grifols Therapeutics, INC Research, Insmed, KaloBios, Kamada, Mpex Pharmaceuticals, N30 Pharmaceuticals, Nordmark, Novartis, Parion Sciences, Pharmagenesis (Cornerstone 281), Pharmaxis, ProQR Therapeutics, Pulmatrix, PulmoFlow, Respira Therapeutics, Savara Pharmaceuticals and Vertex. MB reports receiving fees for serving on advisory boards for Savara Pharmaceuticals, Vertex, Genentech and Novartis.
Provenance and peer review Not commissioned; internally peer reviewed.