FDA Approves New Drug for a Form of Cystic Fibrosis

Martha Kerr


January 31, 2012

January 31, 2012 — The US Food and Drug Administration (FDA) today approved ivacaftor (Kalydeco, Vertex Pharmaceuticals, Inc) for patients aged 6 years and older who have a rare form of cystic fibrosis (CF) and carry the G551D mutation in the CF transmembrane regulator (CFTR) gene.

Defects in the CFTR gene are the basis of CF. In the G551D mutation, the amino acid glycine in position 551 is substituted with aspartic acid.

"Kalydeco is the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in an FDA release. "This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease."

Ivacaftor was designated as an orphan drug, meaning it affects fewer than 200,000 people in the United States. Today's approval was granted ahead of the company’s April 18, 2012, planned approval date.

CF is the most common fatal genetic disease in white persons and affects about 30,000 people in the United States. Approximately 4%, or 1200 people, carry the G551D mutation.

Approval was based on two 48-month placebo-controlled trials involving 213 patients with CF. One trial included patients aged 12 years and older, the other patients aged 6 to 11 years.

Ivacaftor is taken twice a day with fat-containing food. It is effective only in patients with CF who have the G551D mutation. The most common adverse effects are upper respiratory tract infection, headache, stomachache, rash, diarrhea, and dizziness.

"The FDA reviewed and approved Kalydeco in approximately three months under the agency's priority review program that is designed to expedite the review of drugs. The priority review program uses a six-month review, instead of the standard 10 months, for drugs that may offer significant advances in treatment over available therapy," the agency said in a release announcing the drug's approval.

"Today marks an important milestone in our journey to find a cure for cystic fibrosis," said Robert J. Beall, PhD, president and CEO of the Cystic Fibrosis Foundation, in a statement. "Kalydeco addresses the underlying cause of CF, and the science behind the drug has opened exciting new doors to research and development that may eventually lead to additional therapies that will benefit more people living with CF."

"I think it is crucial that we now have a specific disease-focused rather than symptom-focused therapy for a challenging disease," Andrew F. Shorr, MD, MPH, FCCP, associate chief of the Department of Pulmonary & Critical Care Medicine at the Washington Hospital Center, and associate professor of medicine in the Department of Pulmonary & Critical Care Medicine at Georgetown University in Washington, DC, told Medscape Medical News.

"The basic science that went into the development of the [ivacaftor] molecule is fascinating; it really reflects the first fruits of tailored genetic therapy to arise since the discovery of the various mutations causing CF. Unfortunately, the molecule will only be useful in a small segment of the population. The follow-up data are limited and the initial trial small," he cautioned. "In addition, broad genotyping of the CF population to find those who might benefit from the drug will prove costly."

Dr. Shorr has spoken previously to Medscape Medical News about one of the trials that led to ivacaftor's approval (N Engl J Med. 2011;365:1663-1672).

Dr. Shorr has disclosed no relevant financial relationships.


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