Trikafta was approved on October 22 by the U.S. Food and Drug Administration (FDA). The drug is expected to be a useful treatment for 90% of patients with CF.
Vertex Pharmaceuticals announced the publication of data from two Phase III trials of Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for cystic fibrosis in patients ages 12 and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This deletion is the most common mutation associated with CF. The results were published in both The New England Journal of Medicine (NEJM) and The Lancet.
“The results of the Trikafta studies published in both The Lancet and NEJM are impressive and represent a historic moment in CF care, with the medicine demonstrating improvements in multiple CF outcome measures in clinical trials, while being generally well tolerated,” said Raksha Jain, associate professor, Internal Medicine, Pulmonary and Critical Care, The University of Texas Southwestern Medical Center and lead author of the NEJM article. Jain is also the corresponding author and investigator on The Lancet publication. He is also presenting both studies at the North American Cystic Fibrosis Conference being held in Nashville this week.
Cystic fibrosis (CF) is a progressive genetic disease that results in persistent lung infections. It is caused by mutations in the CFTR gene, which cause the CFTR protein to behave abnormally. When it doesn’t work correctly, it does not move chloride to the cell surface. Chloride would normally attract water to the cell surface. As a result, the mucus in various organs, in particular the lungs, becomes thick and sticky.
Trikafta was approved on October 22 by the U.S. Food and Drug Administration (FDA). The drug is expected to be a useful treatment for 90% of patients with CF. The drug was approved for people ages 12 years and up who have at least one F508del mutation in the CFTR gene. This is the most common CF-causing mutation, although there are about 2,000 known CF mutations.
“For approximately 6,000 people with CF in the U.S., Trikafta is the first medicine that can treat the underlying cause of their disease,” said Jeffrey Leiden, chairman and chief executive officer of Vertex, at the approval. “I want to personally thank the hundreds of Vertex scientists who have been working on this program for nearly 20 years—many of whom have dedicated their entire careers to changing the course of this disease; the CF Foundation which has provided support, encouragement and help throughout the journey; and most importantly the thousands of patients, caregivers, doctors and advocates who have courageously and persistently worked side-by-side with us to get to where we are today.”
The clinical trial was conducted at 115 sites in 13 countries from June 2018 to April 2019. It involved 403 patients ages 12 and older who were randomized to receive either the combination therapy or a placebo. Lung function was evaluated at four and 24 weeks. The lung function in patients receiving the therapy improved significantly at four weeks and sustained through 24 weeks. Also, lung flare-ups were 63% lower in the treatment group.
The data was used for the New Drug Application (NDA) to the FDA and for the submission to the European Medicines Agency (EMA), which is currently evaluating the submission.
“Following our recent FDA approval of Trifakta in people ages 12 and older who have at least one F508del mutation, the simultaneous publication in NEJM and The Lancet and concurrent presentation at NACFC are further testament to the unprecedented results shown in these studies,” said Reshma Kewalramani, executive vice president, Global Medicines Development and Medical Affairs and chief medical officer at Vertex. “We have made significant progress toward bringing medicines targeting the underlying cause of disease to all people with CF, and we are grateful to all of the individuals and families who put their trust in us and participated in these studies.”
