MedicalResearch.com Interview with: Pierre-Régis Burgel MD, PhD Professor of Respiratory Medicine French National Reference Center for Cystic Fibrosis (coordinator) Cochin Hospital and Paris Descartes University Paris, France MedicalResearch.com: What is the background for this study? How does lumacaftor-ivacaftor differ from other treatments for CF?  Response: Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which acts as a chloride and bicarbonate ion channel across many epithelia. Defective ion transport leads to multiple organ dysfunction, but airway involvement (related to mucus plugging and infection) and malnutrition are among the most important prognostic factors in patients with CF. Over the past decades, symptomatic treatment, including inhaled and systemic antibiotics, nutritional support, pancreatic enzyme replacement, and specialized center care organization have led to major prognostic improvement. More recently, mutation-specific small molecules targeting defective CFTR have been shown to partly restore ion transport in epithelia, which translated into clinical benefits. Phe508del is the most common CFTR mutation with approximately 70% of patients with cystic fibrosis carrying one Phe508del mutation and 40-50% of patients being homozygous for this mutation. Safety and efficacy of lumacaftor-ivacaftor, which partially restores CFTR function, have been reported in phase 3 clinical trials in patients 12 years of age or older who had CF and were homozygous for the Phe508del. Improvement in lung function, reduction in pulmonary exacerbations and a trend towards an increase in body mass index (BMI) led to its approval by the Food and Drug Administration in February 2015 and by the European Medicines Agency in November 2015. However, the magnitude of effect on percent predicted forced expiratory volume in 1 sec (ppFEV₁), the small improvement in nutritional status and the limited use of concomitant treatment for reducing exacerbations have cast doubt on the clinical benefits associated with lumacaftor-ivacaftor, which has not been approved in several countries. The present study is a multicenter (n=47 centers) observational post-marketing study aimed at evaluating the effects of lumacaftor-ivacaftor treatment in a real-life setting in France. All patients who initiated lumacaftor-ivacaftor in 2016 in the French cystic fibrosis reference network, which comprises 47 pediatric and/or adult centers, was performed. Our goal was to examine its safety and effectiveness over the first year of treatment in a large, unselected, population of adolescents (≥12 years) and adults (≥18 years) with CF and Phe508del homozygous mutations.  (more…)