A Powerful New Cystic Fibrosis Drug Shows Promise

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Illustration of a mucus cell

For the first time, cystic fibrosis patients may have a drug that treats the underlying cause of their disease rather than just its symptoms. According to a new clinical trial, the experimental drug helped patients breathe easier, gain healthy weight and cut infections.

Patients taking the new drug, called ivacaftor, showed improvements in lung function and other measures of health two weeks after starting therapy. They also reported feeling a lot better day to day. Those benefits persisted through 48 weeks of the trial, according to data published Thursday in the New England Journal of Medicine.

The drug affects the function of a key protein called CFTR, for cystic fibrosis transmembrane conductance regulator, which goes awry in the inherited, incurable disorder. At the surface of cells, CFTR creates a channel through which chloride ions are transported; that in turn helps regulate the movement of salt and water in tissues and affects hydration.

When genetic mutations interfere with the proper functioning of CFTR in the lungs, it causes the organ to dry and allows the mucus that surrounds cells to become sticky, thick and dehydrated, restricting breathing. The mucus build-up further puts patients at risk for recurrent infections, which over time destroy the lungs.

Cystic fibrosis (CF) also prevents cells in sweat glands from moving chloride efficiently, which results in a build up of salt (sodium chloride) in sweat; that’s why salty skin is a telltale sign of the disease. The condition affects cells in the pancreas and digestive tract as well, interfering with the proper break down and absorption of food. Patients are typically small and have trouble keeping weight on.

Ivacaftor, previously known as VX-770, keeps CFTR channels open at the cell surface, restoring the body’s salt and water balance. “It’s the first time we have developed a therapy directed at the abnormal proteins and showing that it can be corrected,” study author Dr. Bonnie Ramsey, director of the Center for Clinical and Translational Research at Seattle Children’s Hospital and a professor at the University of Washington School of Medicine, told HealthDay. “It has a huge significance for the whole cystic fibrosis community.” About 30,000 Americans have cystic fibrosis.

Used alone, however, the drug helps only 4% to 5% of CF patients whose CFTR gene defect affects the protein’s function at the cell surface. These patients have a mutation called G551D. The more common gene defect, known as ΔF508, which affects more than 90% of patients with cystic fibrosis, prevents the protein from ever getting to the cell surface in the first place. Researchers are now studying whether ivacaftor can be combined with another drug that would first move CFTR to the surface, and then let ivacaftor take over. Results of that trial are expected in 2012.

The current randomized, controlled, double-blinded study involved 161 patients over age 12 who had at least one copy of the G551D mutation. Patients took either ivacaftor or an oral placebo every 12 hours for 48 weeks. Compared with the control group, patients on ivacaftor showed a more than 10% improvement, on average, on tests of lung capacity, and a 55% reduction in “pulmonary exacerbations” — episodes of infection or inflammation that left them unable to work or function, or resulted in hospitalization. By the end of the study, patients taking ivacaftor had also gained an average of 2.7 kg, or nearly 6 lbs., more than the placebo group and reported feeling fewer symptoms of disease. They also had less chloride in their sweat.

It’s too soon to tell whether the drug will help people with CF live longer. Currently, the average life expectancy for cystic fibrosis patients is about 37 years.

The study was partially funded by ivacaftor’s manufacturer, Vertex Pharmaceuticals Inc., which will market the drug under the brand name Kalydeco if it is approved by the U.S. Food and Drug Administration. Vertex has applied for fast-track approval, which could happen in 2012.

Meredith Melnick is a reporter at TIME. Find her on Twitter at @MeredithCM. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.