Orkambi, developed by Vertex Pharmaceuticals, in the first disease-modifying therapy in Canada for children ages 2 to 5 with CF. It previously was approved in the country for patients with two F508del mutations starting at age 6.
“We believe it is important to treat the underlying cause of cystic fibrosis as early as possible and are committed to expanding treatment options for young children,” Reshma Kewalramani, MD, Vertex’s executive vice president and chief medical officer, said in a press release.
Kewalramani added that Orkambi’s approval in young children “is a testament to how far we’ve come on our goal to bring effective medicines to all people living with CF,” as is ongoing work on potential new treatments.
Health Canada based it decision on data from an open-label, multicenter, Phase 3 trial (NCT03125395) assessing the safety, tolerability, and pharmacological profile of Orkambi in 60 CF patients ages 2 years and older with F508del mutations — the most common CF mutation — in the two CFTR gene copies. (Children with CF inherit one CFTR copy from their father and the other from their mother).
In the trial, patients received Orkambi every 12 hours. Those younger than 6 years took 100 mg lumacaftor/125 mg ivacaftor if they weighed less than 30 pounds (14 kg), or 150 mg lumacaftor/188 mg ivacaftor if they weighed 30 pounds or more. Those age 6 or older were treated with 200 mg lumacaftor/250 mg ivacaftor regardless of their weight.
Results after 24 weeks of treatment showed Orkambi was generally well-tolerated by children ages 2 to 5, with a similar safety profile to that seen in patients ages 6 to 11.
Orkambi lowered the levels of sweat chloride, a measure frequently used to diagnose CF, as patients often have more chloride in their sweat due to the lack of a working CFTR protein. Specifically, the team observed a mean decrease in sweat chloride of 31.7 mmol/L from baseline, or study start. Improvements in such growth parameters, such as weight and stature, were also recorded.
The most frequent adverse event reported was cough, observed in 63% of the children. Most were mild or moderate in severity, although four children had serious events — two cases of pulmonary flares, one gastroenteritis, and one constipation — and three discontinued the treatment due to elevated liver function tests.
These results were presented at the 41st European Cystic Fibrosis Society Conference, held in Belgrade in June 2018.
The U.S. Food and Drug Administration approved Orkambi to treat the same group of pediatric CF patients in August. The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, also recommended Orkambi’s approval for these patients in European Union in November. A decision from the European Commission is expected soon, the company said.