August 8, 2018—Yesterday, the US Food and Drug Administration (FDA) approved the use of lumacaftor/ivacaftor for the treatment of the underlying cause of cystic fibrosis (CF) in certain pediatric patients aged 2-5 years.
 
The combination has been approved for use pediatric patients with 2 copies of the F508del-CFTR mutation, the most common genetic form of CF which affects approximately 1300 patients in the US. This combination was previously approved by the FDA for children aged 6 years or older with the same genotype.
 
This combination works in three parts: by increasing mature protein prevalence at the cell surface (lumacaftor), by processing and trafficking mutated F508del CFTR protein, and by enhancing the function of the CFTR protein once it reaches the cell surface (ivacaftor). The oral granule therapy was approved in 2 different weight-based dosing strengths: lumacaftor 100mg/ivacaftor 125mg and 150mg/188mg.
 
Yesterday’s indication was based on a phase 3 open-label safety trial (NCT02797132) of 60 patients, in which the treated younger patients showed a safety and tolerability profile similar to that in patients ages 6 years and older.

Researchers had observed mean decrease of 31.7 mmol/L (95% CI; -35.7 - -27.6) in sweat chloride at week 24 from baseline, as well as changes in key growth parameters.

According to the findings, presented at the 41st European Cystic Fibrosis Society Conference (Abstract WS01.5) in June, the most common adverse event (AE) prevalent in at least 30% of the patient population was cough (63%). Just 4 patients reported serious AEs; 2 being pulmonary exacerbations, and the others being gastroenteritis and constipation. Three patients discontinued treatment due to AEs or elevated liver function tests.

Manufacturers indicated the combination therapy should be available for fulfillment within 2-4 weeks. Full prescribing information for lumacaftor/ivacaftor can be found here. 
 
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Published Online: Wednesday, August 8, 2018