A Healthy Gamble for Cystic Fibrosis

Ten years ago, Dr. Robert Beall was worried that an opportunity to develop new drugs for cystic fibrosis patients was being squandered. The faulty gene that causes the inherited disease had been discovered nearly a decade before. Researchers had made great strides understanding the biological defect, which leads to progressively worse lung disease.

But aside from failed attempts at gene therapy, no drug companies had joined the quest for new treatments. "We were frustrated," says Beall, president of the Cystic Fibrosis Foundation. "Companies only wanted blockbuster drugs, and no one was willing to spend money on cystic fibrosis," a disease that afflicts just 35,000 people in the U.S. But rather than fuming, "I took the biggest gamble I ever made," Beall recalls. If the pharmaceutical industry wouldn't try to develop cystic fibrosis (CF) drugs on its own, the foundation would pay it to do so.

A New Funding Model

Until then, foundations devoted to specific diseases mainly used the donations they received to provide care and support for patients or to fund basic university research that usually didn't focus on drug development. Beall made the controversial decision to get private industry involved. Since then, the Cystic Fibrosis Foundation has handed drug companies $175 million, a figure that could rise to nearly $300 million if the companies reach certain milestones in the assorted projects.

It has taken plenty of patience, but now the bold move is beginning to pay off. In late March, a partner named Vertex Pharmaceuticals (VRTX) released results showing, for the first time ever, that a drug could actually fix the biochemical flaw in some CF patients. "When they showed us the data, it was one of the happiest days of my life," says Beall.

Yet there could be disappointments ahead. The experimental Vertex drug has only been given to 16 patients for just 14 days, so its long-term safety is unknown. In addition, its potential benefit only applies to a small fraction of CF patients. But the results "mean to me that we do have hope of working directly with the abnormal protein to treat the disease," says Dr. Frank Accurso, director of the CF center at the University of Colorado School of Medicine in Denver. Even better, Vertex has developed a second experimental drug that may treat a larger group of CF patients.

Assay Assist

The results, scientists say, prove Beall's gamble was the right move, one that has since been copied by other nonprofit groups. But when Beall first decided to partner with industry, the response was not overwhelming. "I called up five or six companies, but only two even returned my phone call," he recalls. Big Pharma wants drugs that can be used by millions of people, not tens of thousands. Then Beall heard about a company named Aurora Biosciences in San Diego. Its claim to fame: creating biological tests, known as assays, that could be used to screen hundreds of thousands of chemicals to look for drug candidates.

At the time, "we didn't even know if it was possible to make an assay" to look for drugs to treat CF, Beall explains. CF patients have a defect in their cells. Normal cells produce proteins that create channels in their membranes, or outer shells, that enable important substances to enter and leave. Think of them like the gates of a walled city. But for CF sufferers, the gate for chloride ions and other molecules is missing or defective, causing a variety of symptoms. The most dire is that their lungs produce thick mucus that impairs breathing and fosters infections that damage the lungs. The lungs lose function at an average rate of about 2% per year. "So by age 30, patients have lost 60% of lung function," says Beall. Life expectancy has been increasing thanks to treatments for the mucus and infections, but the average sufferer still succumbs before age 40.