Beating Cystic Fibrosis

It started out like any other day for Emily Schaller. A good hair day, even. And then, there it was: a single gray hair.

Plucking the hair and others that soon followed was more than just humbling rite of passage for Schaller. On the cusp of turning 30, it meant that she had, for the time being, beat the odds stacked against her since she was diagnosed with cystic fibrosis (CF) as an infant.

“If not dying young means I have a full head of gray, I’ll take it,” said Schaller.

Schaller, now 31, is among the estimated 30,000 Americans who are living with CF, a fatal genetic disease that gums up the lungs with unusually thick, sticky mucus, leading to serious respiratory infections. The repeated infections cause decreased lung function, lung damage, and, eventually, lung failure. The mucus also clogs the pancreas, so the body cannot properly digest or absorb food, leading to malnutrition.

CF is caused by inheriting a mutated CFTR gene (and the errant protein it produces) from each parent. Normally, the healthy CF gene makes a protein that is found in the cells that line various organs. This protein controls the movement of chloride and sodium (components of salt) in and out of these cells. In people with CF, the protein is defective, causing the salt balance in the body to be disturbed. Because there is too little salt and water on the outside of the cells, the thin layer of mucus that helps keep the lungs free of germs becomes very thick and difficult to move.

In the 1970s, most children with CF never made it through elementary school. By the early 1980s, when Schaller was diagnosed at 18 months old, children with CF were not expected to live beyond their eighteenth birthday. Though some people with CF still succumb to the disease as a child or young adult, the median life expectancy of someone with CF is closing in on 40 years old—a figure that is expected to increase.

Like most adults living with CF, Schaller admits she grew up thinking she would not live as long as her classmates. But with the development of new drugs and airway clearance techniques that are helping to make cystic fibrosis a manageable disease, she’s a drummer, a triathlete, and the CEO of Rock CF, a Denver-based non-profit organization aimed at improving quality of life for people with CF through exercise.

Having outlived her prognosis, she has found herself navigating new territory was wasn't necessarily prepared for. “I worry about things I really never thought I’d have to think about—like health insurance and having an income to support myself and my parents getting older.”

“CF has really transformed from a childhood disease to one in which adults are planning and living out their futures,” said Seth Walker, a pulmonologist who heads up the Adult Cystic Fibrosis Center at Emory University at Atlanta. He estimates that more than half of the CF patients treated at Emory are adults.

That shift stems largely from the introduction of new strategies to manage the disease. One approach is chest therapy that clears the airways of mucous before it has time to block the airways. Breathing treatments that thin mucous and powerful antibiotics that prevent or control infection are others. And taking pancreatic enzymes can help the body absorb fat and protein. Schaller relies on all three, in addition to a rigorous physical conditioning, to keep the disease in check.

She also is one of a small number of CF patients who are on Kalydeco, the first FDA-approved drug to target the underlying cause of CF—a rare mutation in the CF gene called G551D-CFTR—rather than symptom management. Kalydeco, developed by Vertex Pharmaceuticals in Cambridge, Massachusetts, was designed to correct the function of the defective protein made by the CF gene. It allows chloride and sodium to move properly in and out of cells lining the lungs and other organs.

So far, researchers have found 1,900 mutations in the CFTR gene, 127 of which are known to cause CF. The one targeted by Kalydeco is present in an estimated four percent of CF patients. For the precious few who bear the mutation, Kalydeco increases lung strength by more than 10 percent when compared with patients taking a placebo. Kalydeco also results in fewer infections and an average weight gain of seven pounds, a significant amount for patients who typically have trouble retaining weight.

“As soon as I started the drug, I could tell I was getting better,” says Schaller, who started Kalydeco in 2010 as part of a clinical trial of the drug. Before Kalydeco, Schaller was hospitalized with lung infections so often—at least two or three times a year—that she lost count. Now, “I can get a cold and it won’t knock me down. I recover like a normal person,” she said. “On some days I actually feel like ‘this is what it must be like to live without CF.’”

For patients like Schaller, Kalydeco is a “gamechanger,” said Robert J. Beall, president and CEO of the Bethesda, Maryland-based Cystic Fibrosis Foundation. The organization provided $75 million to Vertex to support the drug’s research and development. In return, the foundation get revenues from the drug’s sale. It just fetched $150 million for a portion of its royalty rights—money Beall says the foundation is reinvesting in the discovery and development of therapies, like Kalydeco, that offer definitive control of the disease.

Though it is too early to consider Kalydeco a cure—its long-term effect remains unknown—it has meant that Schaller and the precious few others who share the mutation have more reason than ever to be optimistic about their future. “I feel no limits, only possibilities. I can’t wait for other people with CF to feel that,” she said.

And they may soon get a chance. With support from the Cystic Fibrosis Foundation, Vertex is now conducting a Phase III clinical trial—the last phase of experimental testing—of Kalydeco in combination with another potential therapy, VX-809, that targets the root cause of the disease, the Delta F508 mutation, in about 50 percent of all people with CF.

Earlier trials have already shown the cocktail significantly improves lung function—so much so that the FDA granted it its Breakthrough Therapy Designation, a designation that allows for accelerated testing and faster review. If the treatment is approved by the FDA, the cocktail could keep the disease at bay in half of all people with CF, as Kalydeco has done for Schaller.

There are other potential drugs on the horizon. Another drug for patients with Delta F508 mutation recently entered clinical trials. And the Foundation has research collaborations underway with Pfizer, Genzyme and other pharmaceutical companies to therapies counter other cystic fibrosis mutations.

The hope, Walker says, is to begin to make CF a chronic, even curable disease, one mutation at a time. “We’re beginning to hit the disease where it begins instead of just treating its symptoms. I don’t think it’s too far in the future where there will be one or two combination treatments like this that will help most people with CF,” he said. “In 10 years, I believe that almost everyone with CF will have a drug that will like insulin is for diabetics.”