How effective is Kalydeco(ivacaftor)?

Kalydeco (ivacaftor) has significant efficacy and can help the CFTR gene to produce better protein functions and improve lung function and other aspects of CF, such as weight gain. It has shown good efficacy and safety in clinical trials.

About Kalydeco(ivacaftor)

It is produced for Boston-based Vertex Pharmaceuticals Inc. and is indicated for the treatment of cystic fibrosis (CF) patients who have a mutation in the CFTR gene and are responding to drug treatment.

If a patient's genotype is unknown, an FDA-approved cystic fibrosis mutation test should be used to detect the presence of a CFTR mutation and then verified using bidirectional sequencing as recommended in the mutation test instructions for use.

Kalydeco(ivacaftor)

Kalydeco was evaluated in 2 randomized, double-blind, placebo-controlled clinical trials in 213 clinically stable CF patients (109 receiving Kalydeco 150 mg twice daily) in CF patients with the CFTR gene G551D mutation.

Trial 1 evaluated 161 patients with CF aged 12 years or older who had an FEV1 of 40-90% predicted at screening, and trial 2 evaluated 52 patients aged 6-11 years with an FEV1 of 40-105% predicted at screening. Patients in both trials were randomized to receive 150 mg of Kalydeco or placebo every 12 hours with a fatty meal for 48 weeks, in addition to prescribed CF treatments (such as tobramycin, Daphne alfa).

The primary efficacy endpoint in each case was improvement in lung function, determined by the mean absolute change from baseline in predicted predose FEV1 percent over 24 weeks of treatment.

Treatment with Kalydeco resulted in significant improvements in FEV1 in both studies, with treatment differences in mean absolute change in percent predicted FEV1 from baseline to week 24 being 10.6 percentage points and 12.5 percentage points between Kalydeco and placebo in Trial 1 and 2, respectively, and these changes were sustained through week 48.

Improvements in the percentage of predicted FEV1 values were observed regardless of age, disease severity, and gender. Indicators of respiratory symptoms associated with CF patients, such as cough, sputum production, and dyspnea, were also improved, which can help the CFTR gene to make proteins that function better and improve lung function.

Clinical study of Kalydeco (ivacaftor) in the treatment of cystic fibrosis

Research background: Cystic fibrosis is a life-limiting disease caused by defective or insufficient activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Phe508del is the most common CFTR mutation.

Research Methods: Two phase 3, randomized, double-blind, placebo-controlled studies were conducted to evaluate the effect of the CFTR corrector lumacaftor (VX-809) combined with the CFTR enhancer ivacaftor (VX-770) in patients 12 years of age or older with cystic fibrosis and homozygous for the Phe508del CFTR mutation.

Patients were randomly assigned to receive lumacaftor (600 mg once daily or 400 mg every 12 hours) plus ivacaftor (250 mg every 12 hours) or matching placebo for 24 weeks.

Study Results: A total of 1108 patients were randomized and received study drug, with a mean baseline FEV1 of 61% of predicted value. In both studies, the primary endpoint was significantly improved in both lumacaftor-ivacaftor dose groups, with differences between active treatment and placebo ranging from 2.6 to 4.0 percentage points in terms of mean absolute improvement in percent predicted FEV1, corresponding to a mean relative treatment difference of 4.3% to 6.7%.

The pooled analysis showed that the lumacaftor + ivacaftor group had a 30% to 39% lower rate of pulmonary exacerbations than the placebo group, and the lumacaftor + ivacaftor group also had lower rates of events leading to hospitalization or the use of intravenous antibiotics.

Study Conclusions: These data suggest that lumacaftor combined with ivacaftor is beneficial in patients with cystic fibrosis who are homozygous for the Phe508del CFTR mutation.

Kalydeco(ivacaftor)

Available as tablets or oral granules and taken twice daily with fat-containing food, it helps the protein produced by the CFTR gene work better, thereby improving lung function and other aspects of cystic fibrosis, including weight gain.

1. Adults and children aged 6 years and above: The recommended dose is 150 mg, that is, one tablet at a time, taken orally every 12 hours, and the total daily dose is 300 mg (2 tablets).

2. Pediatric patients from 2 months to < 6 years old: need to take oral granules. The recommended dosage needs to be analyzed based on body weight. For example, children between 1 and 2 months old, weighing 3kg or more, need to take 1 packet every 12 hours. Children 4 months to 6 months old, weighing 5kg or above, should take 1 packet every 12 hours.

Adverse reactions of Kalydeco(ivacaftor)

The most common ones include headache, oropharyngeal pain, upper respiratory tract infection, rash, nasal congestion, nasopharyngitis, diarrhea, nausea, abdominal pain, dizziness, etc. Corresponding measures can be taken according to the severity of adverse reactions, such as dose reduction, drug withdrawal, etc. Specific measures should be determined based on the patient's specific situation and the doctor's recommendations.

During treatment with Kalydeco, regular physical examinations and laboratory tests should be performed to detect and deal with adverse reactions in a timely manner.

References:

Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17. PMID: 25981758; PMCID: PMC4764353.

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