The European Medicines Agency (EMA) has validated Vertex Pharmaceuticals’ application seeking approval for its triple combination — elexacaftor (VX-445), plus tezacaftor, and ivacaftor (Kalydeco) — for cystic fibrosis (CF) patients who cannot use other approved CF disease-modifying treatments or don’t benefit from them as intended.
This decision comes days after the U.S. Food and Drug Administration approved the triple therapy, marketed under the name Trikafta, for patients with the most common CF-causing mutation, that of at least one F508del defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, found in an estimated 90% of all people with this disease.
AURORA F/MF (NCT03525444) enrolled 403 patients with CF caused by one F508del and one minimal function mutation, who were treated with either the triple combination or placebo for up to 24 weeks. In the AURORA F/F trial (NCT03525548), 107 people with two F508del mutations were treated for four weeks with either the triple combo or Symdeko (tezacaftor/ivacaftor, ivacaftor; known as Symkevi in the European Union).
Results from both studies indicated that triple-combination treatment significantly improved lung function, as assessed by the percent predicted forced expiratory volume in one second (ppFEV1). This was the primary goal of each study. ppFEV1 increased on average by 13.8 percentage points in the 24-week trial, and by 10 percentage points in the four-week trial.
Use of the triple combination therapy also resulted in significant improvements in all of the AURORA F/MF trial’s secondary goals. This included a lower annual rate of pulmonary exacerbations and reduced levels of chloride in patient’s sweat.
The treatment regimen was generally well-tolerated in both clinical trials.
This triple combination therapy is a CFTR modulator, as it aids the defective CFTR protein to work more effectively. Elexacaftor and tezacaftor work as correctors to increase the cell surface levels of functional CFTR by correcting the abnormal F508del mutated protein. Ivacaftor works as a potentiator by improving how well CFTR functions.
“Today marks a significant milestone towards our efforts to bring new medicines to more people around the world who are living with cystic fibrosis,” Reshma Kewalramani, MD, the executive vice president and chief medical officer at Vertex, said in a press release.
“We are looking forward to working with the EMA on this important application,” Kewalramani added.
CF News Today recently had the opportunity to interview Jeffrey Leiden, Vertex’s chairman, president, and CEO. For more information about this triple combo therapy and its approval as Trikafta in the U.S., please our interview using this link.