Vertex to Request Approval of Orkambi as CF Therapy for Young Children in EU

Children with cystic fibrosis (CF) who carry the F508del mutation in both CFTR gene copies showed improved lung function after treatment with Orkambi (ivacaftor/lumacaftor), according to results in a Phase 3 study developed by Vertex Pharmaceuticals.

The study, in pediatric patients ages 6–11, evaluated the effect of Orkambi (200 mg lumacaftor and 250 mg ivacaftor, every 12 hours) in 103 children compared to that of placebo (101 children).  Lung function at baseline was assessed by the percentage of predicted forced expiratory volume in one second (ppFEV1).

After the 24 weeks of treatment, patients in the Orkambi group achieved a positive change in lung clearance index (LCI2.5, a measure of lung function), showing significant improvement in lung function compared to those given placebo. This change was the study’s primary endpoint, or goal.

Treated patients also showed a significant reduction in sweat chloride, assessed by the average absolute change from baseline at day 15 and again after one month, as well as improvements — although not statistically significant — in body mass index and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.

Orkambi was also found to be well-tolerated and to have a safety profile similar to that seen in a previous Phase 3 trial in children. In this study, only three patients discontinued treatment.

“CF is a progressive disease that begins at birth, and traditional measurements do not always detect the early lung damage that occurs in children,” said Felix Ratjen, MD, the study’s senior author, in a news release. “LCI is a sensitive measure of lung function, and these new data demonstrate that treating children early with ORKAMBI can improve lung function.”

Based on these results, Vertex  is planning to submit a Marketing Authorization Application (MAA) line extension to the European Medicines Agency (EMA) — the European Union’s regulatory agency for medicines — for the use of Orkambi in this pediatric population. Orkambi recently received similar approval from the U.S. Food and Drug Administration (FDA) following positive results in a Phase 3 trial in children. It is already approved for CF patients 12 and older with two copies (one inherited from each parent) of the F508del mutation in the CFTR gene.

“This study is an important complement to recently presented long-term data in patients 12 years and older suggesting ORKAMBI may modify the course of CF,” Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex, said in the release. “These new data demonstrate that treating the underlying cause of the disease with ORKAMBI improves lung function in even younger patients.

“We are preparing to submit these important data to the EMA in the first half of 2017, and we look forward to bringing ORKAMBI to eligible children in Europe as soon as possible,” Chodakewitz concluded.

It is estimated that, in Europe, approximately 3,400 children ages 6 through 11 have two copies of the F508del mutation in the CFTR gene, which is the gene defective in CF patients.