Study shows new medication effectively treats underlying cause of cystic fibrosis

A new study has confirmed that the drug, ivacaftor (VX-770), significantly improves lung function in some people with cystic fibrosis (CF). The results of the phase III clinical trial study, “A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation,” led by Bonnie W. Ramsey, MD of Seattle Children's Research Institute and the University of Washington, were published today in the New England Journal of Medicine.

Ivacaftor, also known as VX-770, was developed by Vertex Pharmaceuticals with financial support from the Cystic Fibrosis Foundation. The oral medicine targets the defective protein produced by the gene mutation called G551D that causes CF. Researchers found that patients carrying G551D – approximately four per cent of all CF patients – who were treated with VX-770 showed a 17 per cent relative improvement in lung function that was sustained over the course of 48 weeks.

Additionally, patients with G551D treated with VX-770 showed improvements in other areas critically important to the health of people with CF. Study participants experienced significant reductions in sweat chloride levels indicating an improvement in the body's ability to carry salt in and out of cells – a process which when defective leads to CF. They also experienced decreased respiratory distress symptoms and improved weight gain. Those who received VX-770 gained on average seven pounds compared to those in the placebo group who gained approximately one pound. This is significant because many people with CF have difficulty gaining and maintaining weight due to reduced lung function and chronic infection.

“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 VX-770,” said Dr. Ramsey, director of the Center for Clinical and Translational Research at Seattle Children's Research Institute and endowed chair in Cystic Fibrosis (CF) in the Department of Pediatrics at the University of Washington School of Medicine.

Dr. Ramsey and co-investigators evaluated lung function in patients 12 years or older who carry at least one copy of the G551D mutation. The study included 161 patients at multiple healthcare centers who received at least one dose of VX-770 or placebo. The study is the third and final in a series designed to assess VX-770's effectiveness and safety before it is approved for public use.

Approximately 30,000 children and adults in the United States and 70,000 people worldwide have CF. The disease is caused by a defective gene that affects many parts of the body, but is especially harmful to the lungs and pancreas. The gene mutation causes very thick, sticky mucus to clog the lungs and often cause life-threatening infections. In the 1950s, few children with CF lived beyond age five. Today, advances in research and medical treatments have made it possible for people with CF to live well into their 30s, 40s and beyond.

Co-investigators of this study in the Washington region are: Moira Aitken, MD, professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Washington Medical Center and Ronald Gibson, MD, PhD, director of the Cystic Fibrosis Clinical Center at Seattle Children's Hospital and professor of pediatrics at the University of Washington School of Medicine.

Other co-investigators of the study include: Jane Davies, MD, MB, ChB from the Respiratory Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London; N. Gerard McElvaney, MD from the Royal College of Surgeons and Beaumont Hospital, both in Dublin; Elizabeth Tullis, MD from St. Michael's Hospital, University of Toronto; Scott C. Bell, MB, BS, MD from the Department of Thoracic Medicine, Prince Charles Hospital and Queensland Children's Medical Research Institute, University of Queensland in Brisbane, Australia; Pavel Dřevínek, MD from the Department of Pediatrics, 2nd Medical School, Charles University, Prague, Czech Republic; Matthias Griese, MD from Dr von Haunersches Kinderspital, University of Munich, Munich, Germany; Edward F. McKone, MD, from St. Vincent's University Hospital in Dublin; Claire E. Wainwright, MD, MB, BS from St. Vincent's University Hospital in Dublin and the Queensland Children's Medical Research Institute, University of Queensland in Brisbane, Australia; Michael W. Konstan, MD from Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland; Richard Moss, MD from Stanford University School of Medicine, Stanford, CA; Felix Ratjen, MD, PhD from the University of Toronto Department of Pediatrics and Hospital for Sick Children in Toronto; Isabelle Sermet-Gaudelus, MD, PhD from the Centre d'Investigation Clinique–Hôpital Necker, Paris; Steven M. Rowe, MD, MSPH from the University of Alabama at Birmingham, Birmingham; Qunming Dong, PhD, Sally Rodriguez, PhD, Karl Yen, MD and Claudia Ordoñez, MD from Vertex Pharmaceuticals, Cambridge, MA; and J. Stuart Elborn, MD from the Centre for Infection and Immunity, Queens University Belfast, Belfast, United Kingdom.

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At the forefront of pediatric medical research, Seattle Children's Research Institute is setting new standards in pediatric care and finding new cures for childhood diseases. Internationally recognized scientists and physicians at the Research Institute are advancing new discoveries in cancer, genetics, immunology, pathology, infectious disease, injury prevention and bioethics. With Seattle Children's Hospital and Seattle Children's Hospital Foundation, the Research Institute brings together the best minds in pediatric research to provide patients with the best care possible. Children's serves as the primary teaching, clinical and research site for the Department of Pediatrics at the University of Washington School of Medicine, which consistently ranks as one of the best pediatric departments in the country. For more information, visit http://www.seattlechildrens.org/research.

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