European Commission: approval for Kalydeco, the first medicine to treat the underlying cause of cystic fibrosis in people with G551D mutation
Vertex Pharmaceuticals has announced that the European Commission has approved Kalydeco ( Ivacaftor ) for patients with cystic fibrosis ages 6 and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene.
Kalydeco is the first medicine to target the underlying cause of the disease in these patients.
Cystic fibrosis is a rare genetic disease caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. In people with the G551D mutation, Kalydeco helps the defective CFTR protein function more normally.
An estimated 1,100 people in Europe have the G551D mutation.
The European Commissions decision is based on positive findings from two global Phase 3 studies in which Kalydeco has demonstrated significant and sustained improvements in breathing, weight gain and other measures of disease for people ages 6 and older with this specific genetic mutation, compared to placebo.
In addition, people who took Kalydeco were 55% less likely to have pulmonary exacerbations, or periods of worsening in the signs and symptoms of the disease that often require treatment with antibiotics and hospital visits, than those who received placebo.
Fewer people in the Kalydeco treatment groups discontinued treatment due to adverse events than in the placebo groups. The majority of the adverse events associated with Kalydeco were mild to moderate.
Adverse reactions very commonly observed in those taking Kalydeco included headache; upper respiratory tract infection including sore throat and nasal congestion; rash; diarrhoea; and abdominal pain.
Two patients in the group receiving Kalydeco reported a serious adverse reaction of abdominal pain.
Kalydeco ( 150mg, q12h ) was first approved by the U.S. Food and Drug Administration in January 2012, for use in people with cystic fibrosis ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.
Kalydeco is not effective in patients with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene. Therefore, use of Kalydeco in these patients is not recommended.
Kalydeco is contraindicated in any patient with hypersensitivity to the active substance or to any of the excipients.
Moderate elevations in liver function tests ( transaminases ) are common in subjects with cystic fibrosis. Overall, the incidence and clinical features of transaminase elevations in clinical trials was similar between subjects in the Ivacaftor and placebo treatment groups. In the subset of patients with a medical history of elevated transaminases, increases have been reported more frequently in patients receiving Kalydeco compared to placebo. Therefore, liver function tests are recommended prior to initiating Kalydeco, every 3 months during the first year of treatment, and annually thereafter. Patients who develop unexplained increased transaminase levels during treatment should be closely monitored until the abnormalities resolve and consideration should be given to the continuation of treatment after assessment of the individual benefits and risks.
Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Medicinal products that inhibit or induce CYP3A activity, may impact the pharmacokinetics of Ivacaftor. Ivacaftor is a weak CYP3A inhibitor and may modify the pharmacokinetics of medicinal products metabolised through the CYP3A system.
In vitro studies have indicated that Ivacaftor has the potential to inhibit P-glycoprotein ( P-gp ) and CYP2C9. The dose of Kalydeco must be adjusted when concomitantly used with potent and moderate CYP3A inhibitors. Exposure to Ivacaftor is reduced by the concomitant use of CYP3A inducers, therefore potentially resulting in loss of efficacy of Kalydeco.
Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 70,000 people worldwide including 30,000 people in the United States, 35,000 in Europe, 3,800 in Canada and nearly 3,000 in Australia. Today, the median predicted age of survival for a person with cystic fibrosis is approximately 38 years in the United States and 41 years in the United Kingdom, but the median age of death remains in the mid-20s. There are more than 1,800 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to cystic fibrosis by creating non-working or too few CFTR proteins at the cell surface. The absence of working CFTR proteins results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage.
Source: Vertex, 2012