NEW YORK – The European Commission last Thursday approved Vertex Pharmaceuticals' Kaftrio (ivacaftor/tezacaftor/elexacaftor) in combination with its CFTR activator Kalydeco (ivacaftor) for children with cystic fibrosis ages 2 through 5 years old who have at least one F508del mutation in the CFTR gene.
The oral medication was already approved in the EU for patients ages 6 years and older who have at least one F508del mutation in the CFTR gene. In September, the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use recommended the EC extend the label for this treatment and make it available to younger children with cystic fibrosis.
Following final regulatory approval from the EC, this combination therapy will be available to eligible cystic fibrosis patients in Austria, Denmark, Ireland, Norway, Latvia, and Sweden, where Vertex has existing reimbursement agreements. Vertex said in a statement that it will work with other EU reimbursement authorities to further broaden access.
"As [cystic fibrosis] starts in early childhood and is a progressive disease, it is important to treat people … as early as possible," said Marcus Mall, head of the department of pediatric respiratory medicine, immunology, and critical care medicine at Charité Universitätsmedizin Berlin. "With the approval of Kaftrio for children as young as 2 years, we can now treat young children with a medicine that has the potential to slow disease progression by addressing the underlying cause of the disease."
Kaftrio is designed to increase CFTR function at the cell surface, enabling cells to more effectively remove the mucus that builds up in the lungs of people with cystic fibrosis. In the US, where this regimen is branded Trikafta, regulators expanded the indication to patients as young as 2 years old back in April.
Vertex, which has international headquarters in London, plans to expand Kaftrio's indication even further to include cystic fibrosis patients with rare mutations. On Friday, the EMA validated Vertex's type II variation application for Kaftrio seeking to extend the indication of the therapy combined with Kalydeco to include cystic fibrosis patients at least 2 years old who have Kaftrio-responsive CFTR mutations based on clinical and/or in vitro data, including the N1303K mutation.
In its regulatory application to the EMA, Vertex submitted data from a Phase III randomized, placebo-controlled clinical study in people with rare non-F508del Kaftrio-responsive CFTR mutations. Vertex said in a statement that the study met its primary endpoint and showed that the combination therapy led to rapid, statistically significant, and clinically meaningful improvements in lung function. The safety of the Kaftrio-Kalydeco combination was consistent with what researchers have already seen in other studies.
Vertex also used the US Cystic Fibrosis Foundation Patient Registry and included in its marketing authorization application real-world data from people with cystic fibrosis with non-F508del Kaftrio-responsive CFTR mutations who are receiving commercially available Kaftrio.
The CHMP will now review this application and issue an opinion to the EC.
Vertex plans to seek the same label expansion for the Kaftrio-Kalydeco combination in Australia, Brazil, Canada, New Zealand, and Switzerland. It will also submit to the US Food and Drug Administration data on the regimen's efficacy in patients with a subset of rare mutations, including N1303K and non-canonical splice mutations, which are not currently included in Trikafta's US label.