CF Banner

A new drug – the first to address the underlying cause of cystic fibrosis – signals a breakthrough in treating and managing the disease.

Recently completed international clinical trials, led by Seattle Children’s Dr. Bonnie Ramsey, confirmed that the drug ivacaftor significantly improves lung function in a subset of patients with cystic fibrosis (CF).

Previous treatments improve the quality of life for CF patients, but only address symptoms of the disease. Ivacaftor is the first to address the underlying cause, marking an important milestone in CF research.This compilation of findings is unprecedented in this genetic disease.” ~ Dr. Bonnie Ramsey

For decades, scientists have known that a sluggish flow of salt and water between cells causes the symptoms of CF. Once the CF gene was discovered in 1989, researchers began identifying the gene’s mutations (approximately 1,400 so far). Each mutation results in a unique defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that regulates the flow of salt and water in and out of cells — making the hoped-for one-size-fits-all CF treatment elusive.

Ivacaftor is designed to treat the G551D mutation, which affects only 4% of all people with CF. “We couldn’t have done this study 25 years ago, because we didn't know what the CF mutations were,” says Ramsey. “We would have tested the drug on all CF patients and completely have missed its impact on those with this specific mutation.”

Ivacaftor is an oral medicine developed by Vertex Pharmaceuticals with financial support from the Cystic Fibrosis Foundation. It works by counteracting the defective protein, thus enabling salt and water to flow more freely between cells. As a result, salt balance is restored and lung function improves. Patients in the study were able to breathe more easily, gain weight and get fewer infections.

The trials found that patients showed a significant improvement in lung function after just two weeks of taking ivacaftor. These patients also had fewer CF-related respiratory problems, such as bronchitis and wheezing, during the course of treatment. Perhaps most compelling, 67% of participants taking ivacaftor had not had flares in their respiratory symptoms by the end of the 48-week study. “I’ve been involved with clinical trials for 30 years and I’ve never seen this kind of change sustained this long,” says Ramsey, a national leader in researching cystic fibrosis.

Participants taking ivacaftor were hospitalized less often than the control group and gained an average of 7 pounds during the study. They also had significant reductions in sweat chloride levels, indicating ivacaftor was indeed effective in improving the transport of salt and water between cells. No other drug has yet to improve sweat chloride levels in CF patients.

“Our study shows that we are now able to improve the quality of life for cystic fibrosis patients with the G551D mutation with the administration of ivacaftor,” says Ramsey. “This compilation of findings is unprecedented in this genetic disease.”

A bridge between industry and academics

The success of the study relied in large part on the work done by the coordinating center of the Cystic Fibrosis Therapeutics Development Network (TDN) at Seattle Children’s Research Institute, which supports a nationwide clinical trials network of 77 sites funded by Cystic Fibrosis Foundation Therapeutics, Inc.

CF 220x130The coordinating center worked with Vertex to develop the study design and provided specialized research training and coordination for the participating sites across North America, Europe and Australia. In addition, they developed strategies to ensure timely enrollment into the study despite the challenges of conducting it in a rare disease setting.

“The TDN continues to be a model in how to accelerate research in orphan diseases, such as CF, through the efficient conduct of multicenter trials. The success of the TDN can be attributed to its ability to form a bridge between industry and academics, which ultimately benefits the patient,” says Dr. Nicole Hamblett, who co-directs the TDN.

The future

The results of Ramsey’s study validate decades of CF research and break new ground by providing a foothold for developing additional therapies that get to the root cause of CF.

The next round of clinical trials will use ivacaftor with other medications to find the right combination for treating the vast majority of CF patients, according to Ramsey. “This is just the first step in a major effort by the CF community to develop therapies to treat the CFTR protein dysfunction,” she notes.

The FDA granted accelerated approval of ivacaftor in January 2012. It is marketed under the name Kalydeco.

“The success of the TDN can be attributed to its ability to form a bridge between industry and academics, which ultimately benefits the patient.”
~ Dr. Nicole Hamblett