The US Food and Drug Administration (FDA) has approved a supplemental new drug application allowing use of ivacaftor (Kalydeco, Vertex Pharmaceuticals) in patients aged 6 years and older with cystic fibrosis (CF) who have the R117H mutation in the CF transmembrane conductance regulator (CFTR) gene, the company announced today.

Defects in the CFTR gene are the basis of CF. Ivacaftor was first approved in January 2012 for patients with CF aged 6 years and older with at least one copy of the G551D mutation in the CTFR gene.

With the new approval, the drug is now approved in the United States for use in people aged 6 years and older with CF with any of the following 10 CFTR mutations: R117H, G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.

The approval was based data from a phase 3 study of ivacaftor involving 69 people with CF aged 6 years and older who had the R117H mutation. Roughly 500 people with CF have this mutation in the United States.

"Today's approval marks an important milestone for people with the R117H mutation who will now have a medicine to treat the underlying cause of their disease for the first time," Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex, said in a news release. "We are now one step closer to reaching our goal of providing new medicines to many more people living with [CF]."

Ivacaftor is an oral CFTR potentiator designed to keep CFTR proteins at the cell surface open more often to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

The drug is also approved in Europe, Canada, Australia, and New Zealand to treat people with CF aged 6 years and older with specific genetic mutations in the CFTR gene. The safety and efficacy of ivacaftor in children with CF younger than 6 years have not been established.

Elevated transaminase levels have been reported in patients taking ivacaftor. It is recommended that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels be assessed before starting ivacaftor, every 3 months during the first 12 months of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve, the company notes. Dosing should be interrupted in patients with ALT or AST levels greater than 5 times the upper limit of normal. After resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing, the company advises.

Coadministration of ivacaftor with drugs that are strong CYP3A inducers, such as the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's wort, substantially decreases exposure of ivacaftor and may diminish effectiveness, and is not recommended, the company says. "The dose of ivacaftor must be adjusted when used concomitantly with strong and moderate CYP3A inhibitors or when used in patients with moderate or severe hepatic disease," the company notes.

Cases of noncongenital lens opacities/cataracts have been reported in children up to 12 years of age treated with ivacaftor; baseline and follow-up eye examinations are recommended.

The most common adverse effects associated with ivacaftor include headache; upper respiratory tract infection (the common cold), including sore throat, nasal or sinus congestion, and runny nose; abdominal pain; diarrhea; rash; and dizziness. A complete list of the adverse reactions can be found in the product labeling for ivacaftor.