Ivacaftor, the Miracle Drug?


Ivacaftor has been hailed as a miracle drug for the treatment of Cystic fibrosis (CF). Although Ivacaftor is not designed for every CF sufferer, it is life changing for those who benefit from it.

CF is a genetic disease that affects 70,000 people worldwide and is characterised by an overly viscous mucus lining of the airways, resulting in difficulty in clearing the airways by coughing, and an increase in infections from opportunistic pathogens.  CF is caused by different mutations in the Cystic fibrosis transmembrane conductance regulator (CFTR), an ABC transporter ion channel, which results in an imbalance in ion concentration and the observed phenotype of highly viscous mucus. The CFTR conducts chloride and as well as regulating other ion channels, such as chloride channels and glutathione transport. There are approximately 1900 known mutations within the CFTR, which is primarily expressed within the airway submucosal glands in the lungs.

Until now all CF care has been supportive rather than curative. However a recent breakthrough with the drug Ivacaftor, which treats the underlying problem rather than just the symptoms of CF, could change the CF care landscape. Ivacaftor is used to treat CF patients with one of a set of specific mutations including G551D, which affects approximately 4% of CF patients and is the third most common mutation. The G551D mutation is characterised by correct positioning of the CFTR on the epithelial cell surface but incorrect function, the CFTR is unable to transport chloride ions.

Predicted structure of the CFTR. TMD; Transmembrane Domain, NBD; Nucleotide Binding Domain. The G551D mutation occurs in the NBD2 region and prevents ATP dependent gating. Adapted from Kim and Skach, 2012 (http://dx.doi.org/10.3389/fphar.2012.00201).

Ivacaftor, developed by Vertex Pharmaceuticals together with the Cystic fibrosis Foundation, assists with the function of the mutant CFTR by directly binding the CFTR channel. Binding increases the probability of channel opening by inducing opening of the ion channel independent of ATP binding and hydrolysis. This reduces the imbalance in the ion concentration and lowers the viscosity of the mucus in the airways allowing easier breathing of the CF patient. CF sufferers who have had access to Ivacaftor have been able to “run without coughing” and “take deep breaths”.

The FDA approved Ivacaftor in January 2012 and the combination drug with lumacaftor gained FDA approval in July 2015. The inclusion of lumacaftor in the combination drug enables treatment of CF patients with a slightly different mutation in addition to those treated by Ivacaftor.

However there is a catch, Ivacaftor treatment costs $300,000 per patient per year. Patients are likely to be taking Ivacaftor for the rest of their lives and so the cost becomes astronomical. On the other hand Vertex has stated that they will make the drug available free of charge for those patients in the US without medical insurance and with a household income of less than $150,000 a year.

The real question surrounding Ivacaftor is; how to pay for the miracle?


Source: Kotha and Clancy (2013). Ivacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence. Therapeutic Advances in Respiratory Disease, 7(5)288-296.

Bryony Ackroyd

Twitter: @BryonyAckroyd