There was negligible urinary excretion of ivacaftor as unchanged parent. The apparent terminal half-life was approximately 12 hours following a single dose in the fed state. The apparent clearance (CL/F) of ivacaftor was similar for healthy subjects and patients with CF. The mean (±SD) of CL/F for the 150 mg dose was 17.3 (8.4) L/h in healthy subjects at steady state. Society and culture
Legal status
The U.S. Food and Drug Administration (FDA) approved ivacaftor in January 2012, and soon afterwards so too did the European Medicines Agency (EMA) and Canada and across some European countries.Lumacaftor/ivacaftor was approved by the FDA in July 2015, under breakthrough therapy status and under a priority review. Economics
The cost of ivacaftor is US$311,000 per year, roughly similar to the price of other medications for extremely rare diseases. In the first nine months of its second year on the market (2014), ivacaftor sales were $339M, representing 54% of Vertexs product sales revenue. During the same period, total drug development expenses were $458M, most of which was spent on cystic fibrosis-related research.An editorial in JAMA called the price of ivacaftor "exorbitant", citing the support by the Cystic Fibrosis Foundation in its development and the contribution made by fundamental scientific research performed by the National Institutes of Health and relied upon by Vertex in its cystic fibrosis drug discovery programs.
UK agencies estimated the cost per quality adjusted life year (QALY) at between £335,000 and £1,274,000 —well above the National Institute for Health and Care Excellence thresholds.The medication was not covered under the Ontario Drug Benefit plan until June 2014, when the Government of Ontario and the manufacturer negotiated for what "Ontario Health Minister Deb Matthews had called a "fair price" for taxpayers". The negotiations took 16 months and it was estimated that around 20 Ontarians required the medication at the time.The province of Alberta began covering the medication in July 2014, and in September the province of Saskatchewan became the third province to include it in its provincial medication plan.Delay in agreement on a price for Vertex to charge national health plans led to patient group protests in Wales, England, and Australia.As of March 2016, the combination medication cost $259,000 a year in the United States. Research
The clinical trials used in the regulatory approval of ivacaftor are described here. G551D mutation
Of the approximately 70,000 cases of cystic fibrosis worldwide, 4% (~3,000) are due to a mutation called G551D. The safety and efficacy of ivacaftor for the treatment of cystic fibrosis in patients with this mutation was examined in two clinical trials.The first trial was performed in adults having baseline respiratory function (FEV1) between 32% and 98% of normal for persons of similar age, height, and weight. The baseline average was 64%. Improvement in FEV1 was rapid and sustained.