The Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Kaftrio (ivacaftor/tezacaftor/elexacaftor) in combination with Kalydeco (ivacaftor) as a treatment for 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.
“We are delighted to have received this positive opinion from CHMP,” Carmen Bozic, MD, executive vice president of global medicines development and medical affairs, and chief medical officer at Vertex Pharmaceuticals, said in a press release. Vertex is the developer of Kaftrio, which is approved and marketed in the U.S. as Trikafta.
“If approved, this would be the first CFTR modulator for people with one F508del mutation and one minimal function mutation and would bring additional benefit to people with two F508del mutations,” Bozic added.
In Europe, up to 10,000 CF patients 12 and older have one F508del mutation and one minimal function mutation, according to Vertex.
CF is caused by mutations in the gene CFTR (cystic fibrosis transmembrane conductance regulator), which codes for a protein of the same name. Multiple mutations in CFTR can cause CF, with the most common being F508del — which corresponds to a deletion of a single amino acid from the CFTR protein causing this protein to fold incorrectly and ultimately be degraded before it can reach the surface of the cell.
Vertex’s triple therapy combination consists of multiple CFTR modulators — molecules that act on the CFTR protein so that it can function correctly, either by helping the protein fold correctly or by helping it get to the surface of the cell, where it needs to be to function properly.
Kaftrio will be available as tablets containing 100 mg elexacaftor, 50 mg tezacaftor, and 75 mg ivacaftor. It is intended to be used in combination with an additional 150 mg of ivacaftor (Kalydeco, also marketed by Vertex).
The positive opinion by CHMP, a committee of the European Medicines Agency, was based on the results of two Phase 3 clinical trials: AURORA F/MF (NCT03525444) and AURORA F/F (NCT03525548). Results of these trials demonstrated that the triple combination significantly improved lung function and reduced pulmonary exacerbations in people with CF who have either two F508del mutations (F/F) or one F508del and one minimal function mutation (F/MF).
The trial results also showed the treatment to be generally well-tolerated.
“The clinical data for ivacaftor/tezacaftor/elexacaftor plus ivacaftor in people with CF ages 12 years and older with an F/F or F/MF genotype are unprecedented,” said Marcus A. Mall, MD, professor at Charité University Medical Center Berlin, who was involved in the AURORA trials. “In addition to improvements in lung function, the data have shown improvements in multiple important outcome measures, including quality of life.”
“Both the clinical and patient communities are excited that more people with CF will be able to benefit from CFTR modulators,” Mall added.
“This milestone brings us one step closer to delivering this innovative CF medicine to those who are waiting, and toward our ultimate goal of providing a therapeutic option for every person with this rare and devastating disease,” Bozic said.
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