EMA Validates Application Seeking Expansion of Kaftrio Approval

The European Medicines Agency (EMA) has validated an application that seeks to expand the approval of Kaftrio (ivacaftor/tezacaftor/elexacaftor) in combination with Kalydeco (ivacaftor) to treat cystic fibrosis (CF) in individuals 12 and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and other specific CFTR mutations.

Vertex Pharmaceuticals, which markets Kaftrio, announced the validation of the Type II Variation Marketing Authorization Application (MAA) in a press release.

Kaftrio was approved recently by the European Commission (EC) to treat people 12 and older who have CF caused by either two F508del mutations or one F508del mutation and one minimal function mutation in the CFTR gene. This new application is intended to cover those with one F508del mutation and other types of CF-causing mutations, namely gating mutations.

CF is caused by mutations in the CFTR gene. People have two copies of this gene, one inherited from each biological parent. These mutations lead to the production of a CFTR protein that does not function properly, resulting in a poor flow of salt and water in and out of the cells in a number of organs.

F508del is the most common CF-causing mutation. It has been estimated that about three of every four people with CF in Europe have at least one copy of the CFTR gene with this mutation.

Kaftrio, which is sold under the name Trikafta in the U.S., contains a combination of three CFTR modulators — molecules that make the CFTR protein function more effectively. The therapy is used in combination with Kalydeco, another CFTR modulator sold by Vertex.

Kaftrio’s new MAA is supported by data from a global Phase 3 clinical trial (NCT04058353) sponsored by Vertex. The trial enrolled participants 12 and older with one F508del mutation and either one gating mutation (meaning the “gate” of the CFTR protein gets “stuck closed”), or one residual function mutation (meaning not enough functional CFTR protein gets to the cell’s surface).

Now that Kaftrio’s MAA has been validated, the application will be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the EC. The EC will make a final decision about whether the medication also should be approved for those individuals.