Symkevi-Kalydeco Combo Approved in Europe to Treat CF Patients Ages 6–11

The European Commission has approved the combination of Symkevi (tezacaftor/ivacaftor) and Kalydeco (ivacaftor) for the treatment of children, ages 6 to 11, with cystic fibrosis (CF) carrying certain genetic mutations.

Eligible children must carry either two copies of the F508del mutation — the most common mutation associated with CF — in the CFTR gene, or one copy of the F508del mutation along with one copy of 14 other mutations that are known to nearly eliminate the activity of the CFTR protein. A complete list of all mutations that are amenable to treatment can be found here.

This combination therapy had previously been approved in the European Union to treat CF patients, 12 and older, carrying the same mutations in the CFTR gene.

The European Commission’s decision to approve the combination therapy for younger children was announced shortly after the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency, recommended Symkevi be approved to treat children as young as 6.

“With this approval, children with CF in Europe ages 6 to 11 years with the most common mutation, F508del, have a new treatment option and children with certain residual function mutations will, for the first time, have a treatment option available that addresses the underlying cause of their CF,” Reshma Kewalramani, MD, president and CEO of Vertex Pharmaceuticals, the therapies’ developer, said in a press release.

The combination of Symkevi (known as Symdeko in the U.S.) and Kalydeco will immediately be available to eligible children in Germany, and will soon be available to those living in other European countries, including Denmark, the U.K., and the Republic of Ireland, that have entered into long-term reimbursement agreements with Vertex.

Vertex stated it will work closely with European regulatory authorities to ensure eligible children living in other countries will also have access to the treatment.

“Today’s approval brings us closer to our ultimate goal of providing medicines for all people with CF,” Kewalramani said.

Symkevi and Kalydeco are two CF therapies designed to tackle specific defects in the CFTR protein that prevent it from performing its normal function.

Tezacaftor, one of Symkevi’s active ingredients, is a CFTR corrector designed to counteract the effects of mutations that interfere with the normal folding of the CFTR protein and that prevent the protein from reaching the cells’ surface where it acts as a channel transporting water and chloride in and out of cells.

Conversely, ivacaftor, Kalydeco’s active ingredient, is a CFTR potentiator that is designed to keep the CFTR protein in a stable conformation after it reaches the cells’ surface, to further improve its function.

In Europe, Kalydeco is also approved as a stand-alone therapy to treat infants with CF as young as 6 months. In September, the CHMP also recommended Kalydeco’s approval be extended to allow the therapy to be given to infants as young as four months.