Vertex Pharmaceuticals’ Orkambi (lumacaftor/ivacaftor), a licensed medicine used to treat cystic fibrosis (CF) patients ages 6 and older, has now been approved by the U.S. Food and Drug Administration as the first medicine to treat CF in children ages 2-5.
The approval is for children who have two copies of the F508del-CFTR mutation, the most common gene mutation causing the disease. According to the company, it is estimated that approximately 1,300 children ages 2-5 in the U.S. have this mutation.
Orkambi treatment for these younger children will be commercialized as oral granules instead of the typical tablets to ease ingestion. The oral granules are similar in size to flour particles and should be mixed with 1 teaspoon (5 mL) of soft food or a liquid.
The granules will be available in two doses, 100 mg lumacaftor/125 mg ivacaftor, and 150 mg lumacaftor/188 mg ivacaftor, depending on the child’s weight, to be taken every 12 hours.
Orkambi granules for the new age group should be available within two to four weeks.
“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,” Reshma Kewalramani, MD, executive vice president and chief medical officer of Vertex, said in a press release.
“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,” Kewalramani said.
The FDA’s approval is based on results from a Phase 3 open-label study (NCT03125395) that assessed Orkambi’s safety in CF patients 2 and older with two copies of the F508del-CFTR mutation.
Participants were medicated every 12 hours, according to their age and weight. Patients younger than 6 received 100 mg lumacaftor/125 mg ivacaftor if they weighed less than 30 pounds, and 150 mg lumacaftor/188 mg ivacaftor if they weighed at least 30 pounds. Patients who were 6 or older received 200 mg lumacaftor/250 mg ivacaftor regardless of their weight.
The trial showed that Orkambi was generally safe and well-tolerated for 24 weeks, with children ages 2 to 5 demonstrating a similar safety profile to those who were 6 and older.
One secondary endpoint of the study, the levels of sweat chloride, a parameter commonly used to diagnose the disease, improved after 24 weeks of treatment. Other secondary endpoints, including growth parameters, also improved with the medication.
The most common adverse event reported was cough, affecting 63% of the children in the cohort. Although four children experienced serious adverse events (including pulmonary exacerbations, gastroenteritis, or constipation), and three discontinued the treatment due to those events or elevated liver function tests, most of the adverse events reported were mild or moderate.
“Cystic fibrosis is a systemic, multi-organ, progressive disease that is present from birth,” said John McNamara, MD, medical director of the CF program at Children’s Minnesota Hospital and principal investigator of the study.
“Research suggests Orkambi could impact CF outcomes in patients as young as 2 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,” he said.
Vertex submitted a Marketing Authorization Application extension for Orkambi in children ages 2 to 5 to the European Medicines Agency (EMA), so that the medicine would be available in Europe. That decision is expected in the first half of 2019.