Cystic fibrosis is caused by mutations in a gene known as CFTR. As a result of the mutations, the body experiences a poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients, eventually leading to death. The median age of death is in the early 30s. The disease affects about 30,000 people in the United States.
The 1989 discovery, by two academic laboratories that included Francis S. Collins, now director of the National Institutes of Health, identified the cystic fibrosis gene. At first there was optimism about gene therapy — perhaps a cure as simple as an inhaler and a deep breath. But it didn’t work out that way. The problem of delivering the fix was far more difficult. Thus began a long, forbidding slog in drug development. A major role in this hunt was played by the Cystic Fibrosis Foundation, which funded research by Aurora Biosciences, which was later bought by Vertex Pharmaceuticals of Boston. The foundation helped keep the work alive when drug researchers faced blind alleys and disappointments. The NIH contributed with grants to study how the proteins and genes function, among other things.
Now, a new three-drug combination therapy looks quite remarkable, potentially benefiting 90 percent of those with cystic fibrosis. Clinical trials show patient lung function is dramatically improved, and the drug appears to be targeting the genetic root of the disease, not just treating the symptoms.
The Food and Drug Administration has approved the three-drug combination, called Trikafta, from Vertex. It will cost $311,000 a year, although insurers may cover most of it. The high cost, not unusual for drugs treating rare diseases, is driven in part by corporate calculations of return on investment for billions sunk into the research.
The achievement is the result of persistence by patient advocates and scientists, who never threw in the towel, even when the goal seemed impossible. A lot of bake sales went into supporting the quest, and that kind of support is priceless.