The first drug that treats an underlying cause of cystic fibrosis, rather than just the symptoms, was approved by the Food and Drug Administration on Tuesday, more than 22 years after the gene responsible for the disease was first identified.
Cystic fibrosis is caused by a defective gene which causes the body to produce an unusually thick, sticky mucus. This mucus clogs the lungs and obstructs the pancreas and stops enzymes from helping the body break down and absorb food. Patients are prone to infections and progressively lose the ability to breathe.
The drug, called Kalydeco and developed by Vertex Pharmaceuticals, counters the effect of one specific mutation in the gene that accounts for 4 percent — or about 1,200 — cystic fibrosis cases in the United States.
The mutation, called G551D, is in a gene called the cystic fibrosis transmembrane conductance regulator. The CFTR gene regulates the transport of chloride and water in the body. Kalydeco helps the protein made by the CFTR gene function better, which improves lung function and improves other side effects of cystic fibrosis.
“This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease,” Dr. Janet Woodcock, the director of the Center for Drug Evaluation and Research at the F.D.A., said in a statement issued by the agency.
About 30,000 Americans have cystic fibrosis, which is caused by mutations in a gene called CFTR that is responsible for transport of chloride ions across cell membranes. People with the disease tend to have thick mucus in the lungs, which leads to infections and lung damage. Their average life span is 37 years.
Millions of Americans carry the defective CF gene, but do not have any symptoms. That's because a person with CF must inherit two defective CF genes -- one from each parent. An estimated 1 in 29 Caucasian Americans have the CF gene. The disease is the most common, deadly, inherited disorder affecting Caucasians in the United States. Most children with CF are diagnosed by age 2.
The F.D.A. said it based its approval on two placebo-controlled studies involving a combined 213 patients that showed “significant and sustained improvement in lung function.”
Dr. Ahmet Uluer, a pulmonologist at Children’s Hospital of Boston, said that some of his patients in the clinical trials experienced “a significant change in their day-to-day lives,” including a patient who was able to shovel snow for the first time. But he said the drug was not likely to reverse years of accumulated lung damage.
The story behind Kalydeco is a cautionary tale for those who believe the sequencing of the human genome will lead to a bonanza of new drugs. While the gene responsible for cystic fibrosis was identified in 1989, it took many years to figure out exactly how mutations led to the disease and even longer to figure out how to counteract the mutations.
“There are all these different mutations and each of the mutations was causing it to be broken in a different way,” said Eric Olson, vice president for the cystic fibrosis program at Vertex, which is based in Cambridge, Mass.
Attempts at treating the disease using gene therapy — putting correct copies of the gene into the lungs — did not work. But in the 1990s, techniques were developed to screen chemicals to see if they affected ion transport.
Vertex has two other drugs in midstage clinical trials that it hopes will help cystic fibrosis patients with the most common mutation.
Kalydeco is the second drug from Vertex to be approved by the F.D.A. in the last year.
Its drug for hepatitis C, Incivek, approved in May, is on pace to exceed $1 billion in sales in its first 12 months on the market because it increases the cure rate of that disease and shortens treatment time for many patients.
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The drug will be among the most expensive therapies on the market, costing $294,000 a year, according to Lawrence Walsh, a Barclays Capital analyst. He said more expensive drugs include Soliris, which treats a blood disorder and costs $409,500 a year, and Elaprase, which treats a potentially fatal condition that causes mental retardation and costs $375,000 a year.
Like Kalydeco, these drugs tend to provide significant improvements for a small number of patients. For that reason, health plans tend to cover the cost.
Kalydeco was approved for use in patients six-years-old and older. It was approved in about three months and ahead of an April deadline, according to FDA and the company. The company is planning a study of the drug in patients between two years and five years old.