Unified Grocers’ Sue Klug and her teenage daughter Shelby, who suffers with cystic fibrosis, have been longtime supporters of the CF community. Their family has helped host countless fundraisers and raise generous funds for the Southern California chapter of the Cystic Fibrosis Foundation (read more about their efforts here).
The Klugs and other Cystic Fibrosis Foundation supporters received some positive news this month as Vertex Pharmaceuticals Inc. announced that Phase 3 clinical trials of ivacaftor (Kalydeco) in combination with lumacaftor (VX-809) for people with two copies of the F508del mutation of cystic fibrosis showed significant improvements in lung function and other key measures of the disease.
Based on these results, Vertex plans to submit a New Drug Application (NDA) by the end of 2014 to the U.S. Food and Drug Administration (FDA) for review, with possible approval in 2015.
Results from the two 24-week clinical trials mark an important milestone for nearly 50 percent of people with cystic fibrosis—specifically those with two copies of F508del, the most common cystic fibrosis mutation. The potential treatment is the first to combine two pills to address the underlying genetic cause of cystic fibrosis in people with the F508del mutation.
“This is a proud day for the CF community,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. “Many people with CF and their families have been eagerly awaiting these results, and we are thrilled with the outcome. These studies further validate that we are on the right track to getting new and effective treatment into the hands of people with CF who so desperately need them.”
The Phase 3 trials were conducted at approximately 200 clinical trial sites in North America, Europe and Australia. In total, more than 1,100 people with two copies of the F508del mutation, ages 12 and older, participated in the studies.
The trials tested two different doses of the ivacaftor and lumacaftor combination therapy. Compared with those on placebo, participants who took the combination treatment showed significant and consistent improvement in lung function and in other important health measures, including weight gain, and a reduction in the rate of pulmonary exacerbations. Shelby Klug was in the placebo group.
Repairing the defective protein in people with the F508del mutation is a particularly challenging and intricate process. In this mutation, a series of problems prevents the protein from reaching the surface of the cell. Lumacaftor is designed to move the F508del CFTR protein to the cell surface where ivacaftor can improve its function and help increase the normal flow of salt and fluids in and out of the cell.
These trials are the latest example of the Cystic Fibrosis Foundation’s innovative venture philanthropy model, in which the foundation raises and invests millions of dollars in research toward new treatments. This model has led to tremendous advances in the health and quality of life for people with cystic fibrosis. In fact, the life expectancy of a child with cystic fibrosis has doubled in the last 30 years.
Ivacaftor and lumacaftor were discovered by Vertex in collaboration with the Cystic Fibrosis Foundation, which provided substantial clinical and financial support in the development process, including approximately $75 million in research funding. The foundation has since committed another $75 million with Vertex for the discovery of additional cystic fibrosis drugs.
Ivacaftor was approved by the FDA as a stand-alone drug for people with the G551D mutation in 2012, and eligibility for the drug was expanded to people with several other closely related mutations in February 2014.
“Kalydeco’s approval was the essential first step in treating the underlying defect in CF; now, with this promising drug combination, we are taking another critical step forward in making sure that all people with CF have effective treatments, regardless of their mutation,” Beall added. “We will not rest until we reach that goal.”
The foundation continues to pursue the development of other promising compounds that address the basic defect in cystic fibrosis through collaborative efforts with leading biotech and pharmaceutical companies, including Pfizer, Genzyme and others. The exciting gains in cystic fibrosis drug discovery and development have attracted considerable interest from pharmaceutical companies new to the cystic fibrosis field, spurring research and innovative strategies that could speed development of therapies for all people with cystic fibrosis, including those with rare mutations.
In the feature photo at top is Shelby Klug, daughter of Unified Grocers’ Sue Klug.