FDA approves CF treatment

May 15, 2012

FDA approves Ivacaftor and Exenatide extended-release injection.

(Kalydeco, Vertex Pharmaceuticals)

Cystic fibrosis (CF), a disorder of the lungs and other organs that affects about 30,000 people in the United States, is caused by mutations in the gene encoding the CFTR protein. On January 31, FDA approved ivacaftor (Kalydeco) to treat CF in patients 6 years of age and older who have a G551D mutation in the CFTR gene. Approximately 4% of CF patients, roughly 1,200 people, have this mutation.

Efficacy. Ivacaftor's efficacy was evaluated in two 48-week, placebo-controlled clinical trials involving 213 patients with the G551D mutation. One trial evaluated patients 12 years of age and older, and the other evaluated patients between 6 and 11 years of age. In both studies, ivacaftor 150-mg tablets taken twice daily with fat-containing food (along with their other prescribed CF therapies) resulted in significant and sustained improvement in predicted pre-dose FEV1 at 24 weeks (mean absolute change from baseline: 10.6 percentage points, P<.0001 in trial 1 and 12.5 percentage points, P<.0001 in trial 2). These changes persisted through 48 weeks and were observed regardless of age, disease severity, sex, and geographic region. Participants also demonstrated significant reductions in the risk of pulmonary exacerbations and CF symptoms (in trial 1 only), and were associated with gain in body weight (2.7–2.8 kg at week 48).

Safety. The most common adverse reactions (occurring in ≥8% of study participants) were headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, and dizziness. During 48-week, placebo-controlled clinical trials, the incidence of maximum transaminase (ALT or AST) >8, >5, or >3 times the upper limit of normal (ULN) was 2%, 3%, and 6% with ivacaftor and 2%, 2%, and 8% with placebo. Patients who develop increased transaminase levels should be closely monitored until abnormalities resolve. Ivacaftor should be interrupted in patients with ALT or AST of >5 times the ULN.

Dosage. The recommended dose of ivacaftor for both adults and pediatric patients 6 and older with the G551D mutation is one 150-mg tablet taken orally every 12 hours with fat-containing food (e.g., eggs, butter, peanut butter, cheese, etc.). The dose should be reduced to 150 mg once daily for patients with moderate hepatic impairment (Child-Pugh Class B), and used with caution in patients with severe hepatic impairment (Child-Pugh Class C) at a dose of 150 mg once daily or less frequently. When ivacaftor is co-administered with a moderate or strong CYP3A inhibitor, the dose should be reduced to 150 mg once daily and 150 mg twice-a-week, respectively.