FDA approves ivacaftor to treat rare form of cystic fibrosis

FDA approved ivacaftor (Kalydeco, Vertex Pharmaceuticals) for the treatment of a rare form of cystic fibrosis (CF) in patients aged 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene.

CF is a serious genetic disorder affecting the lungs and other organs that ultimately leads to an early death. It is caused by mutations in a gene that encodes for a protein called CFTR that regulates ion (such as chloride) and water transport in the body. The defect in chloride and water transport results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.

According to Megan Goulart, Vertex Pharmaceuticals company spokesperson, in the phase 3 studies, people treated with Kalydeco experienced significant and sustained improvements in lung function. “In addition, patients treated with Kalydeco were 55% less likely to have a pulmonary exacerbation, which is a period of worsening in the signs and symptoms of the disease that often requires treatment with antibiotics and hospital visits,” Goulart told Formulary. “Pulmonary exacerbations are the leading cause of hospitalizations for people with CF and account for an estimated 50% of the annual medical costs associated with the disease.”

CF, which affects about 30,000 people in the United States, is the most common fatal genetic disease in the Caucasian population. About 4% of those with CF, or roughly 1,200 people, are believed to have the G551D mutation.

“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,” Robert J. Beall, PhD, president and CEO of the Cystic Fibrosis Foundation, said in a Foundation press release.

The FDA reviewed and approved ivacaftor in approximately 3 months under the agency's priority review program, which is designed to expedite the review of drugs.

Ivacaftor was approved ahead of the drug's April 18, 2012, prescription user-fee goal date and is designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the United States.

In patients with the G551D mutation, ivacaftor, a tablet taken 2 times a day with fat-containing food, helps the protein made by the CFTR gene function better and as a result, improves lung function and other aspects of CF such as increasing weight gain.

Two 48-week, placebo-controlled clinical studies involving 213 patients, one in patients ages 12 years and older and another in patients aged 6 years to 11 years, were used to evaluate the safety and efficacy of ivacaftor in CF patients with the G551D mutation. In both studies, treatment with ivacaftor resulted in significant and sustained improvement in lung function.

Ivacaftor is effective only in patients with CF who have the G551D mutation. It is not effective in CF patients with 2 copies of the F508 mutation in the CFTR gene, which is the most common mutation that results in CF. If a patient's mutation status is not known, an FDA-cleared CF mutation test should be used to determine whether the G551D mutation is present.

The most common side effects of ivacaftor include upper respiratory tract infection, headache, stomach ache, rash, diarrhea, and dizziness.