Vertex Pharmaceuticals (Nasdaq: VRTX) today announced that the European Medicines Agency (EMA) has validated a Type II variation application to the Marketing Authorization for KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor. The application is for expansion of the approved indication for KAFTRIO® in a combination regimen with ivacaftor for the treatment of people with cystic fibrosis (CF) ages 2 and above who have a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical and/or in vitro data, including the N1303K mutation. The application will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission regarding the potential approval of this license expansion.
Data to support this submission includes the results of a Phase 3, randomized, placebo-controlled clinical study in people with rare non-F508del KAFTRIO®-responsive CFTR mutations. This study met its primary endpoint and showed that KAFTRIO® in combination with ivacaftor resulted in rapid, statistically significant, and clinically meaningful improvements in lung function compared to placebo (9.2 percentage point increase in ppFEV1; P<0.0001; 95% CI [7.2, 11.3]). The medicine was generally well tolerated, with safety data generally consistent with the established safety profile of KAFTRIO® in combination with ivacaftor.
The Marketing Authorization Application submission package also includes real-world evidence data from the U.S. Cystic Fibrosis Foundation Patient Registry with respect to people with CF with non-F508del KAFTRIO®-responsive CFTR mutations who are receiving commercially available TRIKAFTA® (which is the name for KAFTRIO® in the U.S.). In addition, the submission includes in vitro data using a well-established laboratory model that has been the basis of approval of the rare mutations indication in the U.S.
“It is encouraging to see such positive clinical trial results for KAFTRIO in people with CF with these rare types of mutations, which are non-F508del,” said Professor Isabelle Fajac, Professor of Physiology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France. “The majority of these people currently have no treatment option to address the underlying cause of their CF, so this submission is an extremely important step towards a medicine becoming available for these people with high unmet medical needs.”
“We are committed to going the distance in cystic fibrosis and dedicated to bringing treatments to all people with CF,” said Nia Tatsis, Ph.D., Executive Vice President, Chief Regulatory and Quality Officer at Vertex. “We look forward to working with the EMA on this important submission for people with CF who have non-F508del KAFTRIO-responsive rare mutations, who currently cannot access KAFTRIO for the underlying cause of their disease.”
Vertex plans to submit regulatory filings for the same mutations in Australia, Brazil, Canada, New Zealand and Switzerland. The company also plans to submit a subset of these mutations, including N1303K and non-canonical splice mutations, not currently included in the U.S. TRIKAFTA® label to the U.S. FDA.