FDA approves Orkambi to include use in children ages 2 through 5 years with cystic fibrosis who have two copies of the F508del-CFTR mutation.- Vertex Pharma.

Vertex Pharmaceuticals Incorporated announced the FDA has approved Orkambi (lumacaftor/ivacaftor) to include use in children ages 2 through 5 years with cystic fibrosis (CF) who have two copies of the F508del-CFTR mutation, making it the first medicine approved to treat the underlying cause of CF in this population. Orkambi oral granules are available in two dosage strengths (lumacaftor 100mg/ivacaftor 125mg and lumacaftor 150mg/ivacaftor 188mg) for weight-based dosing. Orkambi oral granules should be available for fulfillment within 2 to 4 weeks.

This FDA approval is based on a Phase III open-label safety study in 60 patients that showed treatment with Orkambi was generally safe and well tolerated for 24 weeks, with a safety profile similar to that in patients ages 6 years and older. Improvements in sweat chloride, a secondary endpoint, were observed at week 24 (mean decrease in sweat chloride from baseline of 31.7 mmol/L; 95% CI: -35.7, -27.6, n=49). Researchers also saw changes in key growth parameters, which were also secondary endpoints in the study. The most common adverse event (?30%) was cough (63%); most adverse events were mild or moderate in severity. Four patients experienced serious adverse events (2 pulmonary exacerbations, 1 gastroenteritis, 1 constipation) and three patients discontinued treatment due to treatment emergent adverse events or elevated liver function tests. These findings were presented at the 41stEuropean Cystic Fibrosis Society Conference in June 2018.

Comment: Orkambi was already approved in the U.S. for the treatment of CF in patients ages 6 and older who have two copies of the F508del-CFTR mutation. A Marketing Authorization Application (MAA) line extension for Orkambi in children ages 2 through 5 years has been submitted to the European Medicines Agency (EMA) with a decision anticipated in the first half of 2019.