FDA approves extended use of cystic fibrosis drug

Victory for Vertex

The U.S. Food and Drug Administration (FDA) has approved the use of Vertex Pharmaceuticals’ ORKAMBI® for 2- to 5-year-old children with cystic fibrosis (CF) who have two copies of the F508del-CFTR mutation. Applicable to 1,300 children with the most common genetic form of the disease, the drug is the first medicine approved to treat the underlying cause of CF in this population.

Cystic fibrosis, a rare, life-threatening genetic disease affecting about 75,000 people in North America, Europe and Australia, is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein stemming from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — in order to have CF.

According to the company, ORKAMBI oral granules come in two dosage strengths (lumacaftor 100mg/ivacaftor 125mg and lumacaftor 150mg/ivacaftor 188mg) for dosing based on weight. ORKAMBI oral granules will be available in a month or less.

As Reshma Kewalramani, M.D., executive vice president and chief medical officer at Vertex, said, “For the first time, children ages 2 through 5 who have the most common form of CF have a treatment for the underlying cause of their disease. We believe it is important to treat the underlying cause of the disease as early as possible, and this approval is another significant milestone in our journey to bring effective medicines to all people living with CF.”

The FDA approval of ORKAMBI was based on a Phase 3 open-label safety study in 60 patients. The study demonstrated that showed treatment with ORKAMBI was generally safe and well tolerated for 24 weeks. Its safety profile was similar to that for patients ages 6 years and older, for whom ORKAMBI was already approved in the U.S. Vertex has applied submitted to the European Medicines Agency (EMA) for a Marketing Authorization Application (MAA) line extension for ORKAMBI in children ages 2 through 5 years, with a decision expected in the first half of 2019.

The Phase 3 study demonstrated improvements in sweat chloride, a secondary endpoint, at week 24 (mean decrease in sweat chloride from baseline of 31.7 mmol/L; 95% CI: -35.7, -27.6, n=49), according to Vertex. Additionally, researchers noted changes in key growth parameters that were also secondary endpoints in the study. The most common adverse event (≥30%) was cough (63%), and most adverse events were mild or moderate. Four patients had serious adverse events, and three patients stopped treatment because of emerging adverse events or elevated liver function tests. Researchers presented these findings at the 41st European Cystic Fibrosis Society Conference in June 2018.

Dr. John McNamara, medical director of the cystic fibrosis program at Children’s Minnesota hospital and lead study researcher, summarized, “Cystic fibrosis is a systemic, multi-organ, progressive disease that is present from birth. Research suggests ORKAMBI could impact CF outcomes in patients as young as two years old. This approval is a significant development that enables physicians to begin treating the underlying cause of the disease in this population earlier than ever before.”