Vertex Triple Combo, Kaftrio, Approved for CF Patients in EU With F508del Mutation

The European Commission (EC) approved Kaftrio (ivacaftor/tezacaftor/elexacaftor) in combination with Kalydeco (ivacaftor) to treat cystic fibrosis (CF) in people 12 and older who have either two F508del mutations or one F508del mutation and one minimal function mutation in the CFTR gene.

The decision follows a positive opinion, supporting approval, by the Committee for Medicinal Products for Human Use, a branch of the European Medicine Agency.

Kaftrio, which is approved and marketed in the U.S. as Trikafta, was developed by  Vertex Pharmaceuticals.

“Today is a significant day for those with CF, their families and Vertex, and one that brings us one step closer towards our ultimate goal of discovering and developing treatments for all patients with CF,” Reshma Kewalramani, MD, CEO and president of Vertex, said in a press release.

CF is caused by mutations in the gene CFTR (cystic fibrosis transmembrane conductance regulator), which encodes an eponymous protein. Many different mutations in CFTR can cause CF; the most common is F508del — a deletion of a single amino acid from the CFTR protein that causes this protein to fold incorrectly and be degraded before it can reach the surface of the cell, where it normally functions.

According to Vertex, as many as 10,000 people in Europe ages 12 years and older have CF characterized by one F508del mutation and one minimal function mutation, or a mutation in which the resulting CFTR protein works minimally. The newly approved triple combination is the first therapy that works on the underlying cause of CF to be approved for such individuals.

At least one F508del mutation is found in about 90% of all CF patients.

Kaftrio consists of multiple CFTR modulators, which act on the CFTR protein so that it can function correctly, either by prompting the protein to fold correctly or by helping it get to the cell’s surface.

The EC’s approval was based on data from two Phase 3 clinical trials: AURORA F/MF (NCT03525444) and AURORA F/F (NCT03525548). Results of the trials showed that Kaftrio significantly improved lung function and lowered pulmonary exacerbations in patients with either two F508del mutations (F/F) or one F508del and one minimal function mutation (F/MF). Results also showed that the treatment was generally well tolerated.

“The clinical data showed significant improvements in lung function and other important measures, such as sweat chloride levels and quality of life as measured by the CFQ-R respiratory domain score, in patients treated with the triple combination therapy. I now look forward to seeing the impact of the medicine in clinical practice,” said Harry Heijerman, MD, PhD, a professor at University Medical Center Utrecht.

Vertex has in place various deals to allow access to Kaftrio through public health programs following EC approval, namely in the U.K. (including England, Scotland, Wales, and Northern Ireland), Denmark, and the Republic of Ireland. There are also provisions for access in other countries.

The company expects eligible patients to have access to Kaftrio “in the upcoming weeks,” and is working with regulatory and governmental bodies to ensure access.

“I would like to thank our dedicated scientists, as well as study investigators and people with CF who participated in our clinical trials to enable this innovative medicine to be approved in Europe today. Without their commitment, this milestone would not have been possible,” Kewalramani added.