The U.S. Food and Drug Administration (FDA) has approved the expanded use of TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for the treatment of cystic fibrosis (CF) in patients aged 2 and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation that is responsive to TRIKAFTA based on clinical and/or in vitro data. This approval adds 94 additional non-F508del CFTR mutations to the TRIKAFTA label, making approximately 300 more people with CF in the U.S. eligible for a medicine that treats the underlying cause of their disease for the first time.
Safety Information Update: The approval also includes an update to safety information, moving warnings about liver injury and liver failure to a boxed warning. This change emphasizes the serious and potentially fatal risks associated with TRIKAFTA, including cases of liver failure leading to transplantation and death reported in both clinical trials and post-marketing settings.
About Cystic Fibrosis: CF is a rare, life-shortening genetic disease affecting more than 92,000 people globally. It is a progressive, multi-organ disease that impacts the lungs, liver, pancreas, GI tract, sinuses, sweat glands, and reproductive tract. The disease is caused by a defective and/or missing CFTR protein resulting from mutations in the CFTR gene.
How TRIKAFTA Works: TRIKAFTA is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface, while ivacaftor facilitates the ability of CFTR proteins to transport salt and water across the cell membrane. This combined action helps hydrate and clear mucus from the airways.
Important Safety Information: Patients and healthcare providers are advised to monitor liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) prior to initiating TRIKAFTA and regularly thereafter. TRIKAFTA should not be used in patients with severe hepatic impairment and is not recommended for those with moderate hepatic impairment unless the benefit outweighs the risk.
Adverse Reactions: Serious adverse reactions, including hypersensitivity reactions and cataracts in pediatric patients, have been reported. Patients should be monitored for signs of liver injury, hypersensitivity reactions, and undergo baseline and follow-up ophthalmological examinations as recommended.