For the better part of two decades, Emily Schaller could barely take a deep breath without lapsing into coughing fits. At the age of 18 months, Schaller was diagnosed with cystic fibrosis, a hereditary disease that chokes the airways with sticky mucus, making victims susceptible to infections and other problems that often kill them before they turn 40. Schaller, now 29, says doctors told her parents, "Enjoy her, because she probably won't live long enough to graduate from high school." By age 13, she was suffering the full effects of the disease, which required her to take various medications and wear a vest that vibrates to loosen her congested lungs.
Then in December 2009, Schaller started taking VX-770, an experimental drug from Vertex Pharmaceuticals (VRTX). Now the self-described exercise enthusiast says she can run 10 to 12 miles with barely any breathing problems. "This past year has been the coolest of my life," says Schaller, who runs the Rock CF Foundation, a nonprofit near Detroit that helps fund research on the disease, which afflicts 30,000 Americans. "It was a whole new feeling that I hadn't felt since I was a little kid."
Vertex's drug is in the third and final stage of testing required for U.S. Food and Drug Administration approval. In a study released in February, Vertex reported that the drug increased breathing function by 10.5 percent over a year, reduced patients' need for antibiotics, and led to an average weight gain of seven pounds. "We were euphoric," says Robert Beall, chief executive officer of the Cystic Fibrosis Foundation in Bethesda, Md., which helped fund development of the Vertex drug. The results "suggest we've already added five years of life to these patients."
The CF gene, discovered in 1989, was one of the first found using new gene-hunting techniques that have led to better understanding of the biology of dozens of illnesses. The genetic research is helping scientists close in on treatments for cancer, diabetes, and other disorders that target glitches that occur during an individual's lifetime. VX-770 is the first pill designed to repair an inherited flaw based on the discovery of the mutation that causes the disease.
Cystic fibrosis is caused by mutations to a gene that, when working properly, creates proteins to help transport fluid in and out of cells. When the gene is defective and the proteins don't work, chloride, a component of salt, can't travel freely across cell membranes. That limits the flow of fluid outside the cell, causing mucus there to dry up and clog airways, allowing bacteria to gather.
VX-770, designed for a mutation carried by 4 to 5 percent of CF patients, enhances the function of the protein, creating a gateway that allows chloride to pass through the cell wall. About 90 percent of people with the disease, though, also suffer from a thornier problem: The protein never makes it to the cell wall. So Vertex is developing a second drug—VX-809—that helps transport the protein to the membrane. "To have optimal benefit, you need two compounds," says Eric Olson, head of Vertex's cystic fibrosis unit. "One to get the protein to the surface, and one to boost its activity once it's out there."
VX-809 is still in a so-called Phase II test as is the combined treatment. While VX-770 could win approval as early as 2012, any formula with both drugs likely won't be available for several years. "The combination therapy down the line is going to be the real driver," says Brian Skorney, an analyst with brokerage ThinkEquity in New York. Such a drug, he says, could eventually generate $1 billion a year in sales. On Feb. 23, when Vertex reported the VX-770 data, the company's Nasdaq-traded shares jumped 15 percent.
The medicines are the fruit of more than a decade of research. After the CF gene was discovered, scientists initially pursued gene therapy, trying to introduce a normal gene into cells to replace the faulty one. When that didn't work, the focus shifted to medicines such as VX-770 that could simply help defective proteins function properly. The Cystic Fibrosis Foundation asked drugmakers if they would screen compounds in their chemical libraries to determine whether one might affect the protein that helps move fluids in and out of cells.
Aurora Biosciences in San Diego agreed to test thousands of chemicals, eventually yielding compounds that led to the Vertex therapies. Vertex bought Aurora in 2001 for about $600 million and maintained the relationship with the CF Foundation, which supplied $75 million in funding for the program. "Discovering the genetic cause of a disease can lead you toward a therapy you never would have thought of otherwise," says Francis Collins, one of the CF gene's discoverers and now director of the National Institutes of Health.
The cystic fibrosis program, once an uncertain part of Vertex's future after the Aurora acquisition, has transformed the company into a diversified drugmaker, says Phil Nadeau, an analyst with Cowen & Co. in New York. Vertex is awaiting regulatory approval for Telaprevir, a medicine for hepatitis C that Nadeau estimates could draw more than $4 billion in annual revenue. "Now people see [Vertex] as more diversified," Nadeau says. "VX-770 is a second pillar the company can stand on."
The bottom line: If approved, Vertex's new cystic fibrosis pill will be the first treatment developed from genetic research for an inherited mutation.