Laura and Cate are now six months into extensions of the ivacaftor clinical studies, which will provide them with the medication for eight years, their mother said. "We're on it until it gets FDA approval."
Vertex Pharmaceuticals, of Cambridge, Mass., developed the drug in collaboration with a non-profit drug research affiliate of the Cystic Fibrosis Foundation. On Oct. 19, Vertex asked the FDA for a priority review of the drug, which can be granted to medications considered major treatment advances. Vertex also requested similar expedited consideration from the European Medicines Agency, the regulatory body for the European Union.
The trial in which Laura enrolled found that ivacaftor improved lung function, helped with normal growth and weight gain, and reduced infections with few side effects, according to a report in today's issue of the New England Journal of Medicine. Improvements for those getting the drug began as early as two weeks and lasted for the duration of the study. At the 24-week mark, participants receiving the drug scored 10.6 percentage points better on a test of their ability to push air out of their lungs than those getting a placebo. By the end of the 48 weeks, those getting the drug had gained, on average, almost six pounds more than those getting a dummy pill. Furthermore, the rate of serious side effects was worse among placebo recipients than those getting ivacaftor, suggesting it's safe as well.
"I've been doing research in Seattle 30 years and this is a really dramatic finding," said lead author Dr. Bonnie W. Ramsey, who holds an endowed chair in cystic fibrosis at the University of Washington School of Medicine and directs the Center for Clinical and Translational Research at Seattle Children's Research Institute. "This is the first time that there has been a drug treating the basic defect, the abnormal protein [of cystic fibrosis]. The changes that have been observed, not only lung function, but reduction in number of respiratory flares, symptoms, weight gain, those have all been dramatic changes."
The drug's experimental success represents "a triumph resulting from the discovery of the cystic fibrosis gene in 1989," Dr. Pamela Davis, of Case Western Reserve University School of Medicine in Cleveland, wrote in an accompanying editorial. However, critical questions remain, such as whether the drug will be safe for infants and younger children and if it can be used preventively, before lung disease develops, she wrote.
Up until now, most drugs given for cystic fibrosis treated only its complications, such as chronic lung inflammation and frequent infections, and helped patients clear the clogged mucus better. These drugs helped push median survival in the last four decades from 11 years to what the Cystic Fibrosis Foundation says is now 37 years.
The disorder results from mutations in the gene for the protein that controls the balance of salt and water in the body's mucus membranes. Ivacaftor, also called Kalydeco, restores the normal balance of salt and water among the 5 percent of CF patients with the G551D mutation, one of hundreds that affect the CFTR (cystic fibrosis transmembrane conductance regulator) gene. About 30,000 Americans have cystic fibrosis.
Ivacaftor, although only helpful to that sub-group of patients, still has great potential, said Dr. Ronald Crystal, chairman of the Department of Genetic Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical College, and chief of pulmonary and critical care medicine. "I would predict for the subset of individuals who have this mutation, that it will prolong their lives."
He said the drug turns a bad protein into a good protein, "taking something that's dysfunctional and making it functional. It's making a silk purse out of a sow's ear." The techniques used to search for the drug have other applications, said Crystal, who was not involved with the study. "This will give further encouragement to pharmaceutical companies to develop drugs for these chronic genetic disorders."
Results from a study of ivacaftor in children ages 6 to 11 (in which Cate participated), as well as use of the drug in combination with VX-809, another drug in the CF pipeline, are being presented this week at the 25th Annual North American Cystic Fibrosis Conference in Anaheim, Calif.