Cystic fibrosis (CF) is a rare, life-threatening genetic disease with a median age of survival between 34 and 47 years of age, however the median age for death is the in mid twenties. CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a protein encoded by the CFTR gene and is an ABC transporter-class ion channel that transports chloride across epithelial cell membranes. To date, there are more than 1,800 known mutations in the CFTR gene. The absence of working CFTR proteins results in a poor flow of salt and water into and out of the cell leading to a buildup of thick mucus. This can affect a number of organs including the lungs. In the lungs it can generate chronic lung infections and progressive lung damage.
Vertex Pharmaceuticals Inc., a global biotechnology company, has announced the results from a Phase 3 clinical trial of ivacaftor (Kalydeco) in patients with the R117H mutation of cystic fibrosis aged 6 and older. The company reports that the study did not demonstrate enough improvement in lung function to meet the primary endpoint. However, participants ages 18 and older did show significant improvement. Vertex plans on discussing the results with the U.S. Food and Drug Administration (FDA).
Ivacaftor was tested on 69 patients with the R117H mutation, including 50 individuals ages 18 and older. Around 300 people with this mutation in the United States are ages 18 and older. According to Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation, “The results from this trial provide valuable information that will help us move forward in our efforts to treat the underlying cause of the disease in all people with CF. While we are disappointed that ivacaftor did not show improvements for the entire group, we are encouraged by the significant gains in lung functions seen in those 18 and older, the group with more advanced lung disease.”
Ivacaftor is the first drug to tackle the underlying cause of Cystic Fibrosis and was approved by the FDA in 2012 to treat patients with the G551D mutation ages 6 and older. It is now being studied in more patients and is also being tested in combination with another possible Cystic Fibrosis therapy, VX-809, in individuals who have two copies of the most common CF mutation, Delta F508.
Kalydeco (ivacaftor) is a CFTR potentiator and is taken orally. It is administered to help the CFTR protein function more normally once it reaches the cell surface. It helps to hydrate and clear mucus from the airways so the patient can breathe better.