The US Food and Drug Administration has officially approved Vertex Pharmaceuticals Incorporated’s therapeutic ALYFTREK.
According to certain reports, the stated drug happens to be a once-daily next-in-class triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator for the treatment of cystic fibrosis (CF) in people 6 years and older who have at least one F508del mutation, or another mutation in the CFTR gene that is responsive to ALYFTREK.
Talk about cystic fibrosis (CF), it is essentially a rare, life-shortening genetic disease that affects more than 92,000 people globally. In essence, the condition translates to a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands, and reproductive tract.
The factors which cause CF include defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes, one from each parent, to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. Basically, CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface.
This defective function and, or absence of CFTR protein, results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, for instance, the condition leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death by CF is in the 30s, but with treatment, projected survival is gradually improving.
More on that would reveal how the stated approval draws its basis from the most comprehensive Phase 3 pivotal program ever conducted for CF, including more than 1,000 patients across more than 20 countries and more than 200 sites. Previously released at the North American Cystic Fibrosis Conference in September of 2024, the trial results showcased that Phase 3 studies in people with CF, aged 12 years and older, met their primary endpoint (non-inferiority on absolute change from baseline in ppFEV1 compared to TRIKAFTA) and all key secondary endpoints.
Furthermore, when it came down to assessing the drug in children with CF aged 6-11 years, ALYFTREK demonstrated safety at the primary endpoint. As for the secondary endpoints, they included absolute change from baseline in ppFEV1 and absolute change from baseline in SwCl, each one supporting the benefit of ALYFTREK.
“In Phase 3 clinical trials, across a broad range of genotypes, once-daily ALYFTREK demonstrated non-inferiority to TRIKAFTA in ppFEV1 response and statistically significant improvement in SwCl, a welcomed advancement for the treatment of CF,” said Claire L. Keating, M.D., Co-Director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University and investigator in the ALYFTREK clinical trial program. “ALYFTREK has the potential to improve the care of patients with CF.”
Another detail worth a mention here is rooted in the fact that ALYFTREK is the first, once-daily CFTR modulator. You see, during a recent survey, approximately 75% of physicians reported that more convenient dosing is a very high unmet need for people with CF. Hence, such people can enjoy better benefits from a once-daily dosing regimen, given the need to take CFTR modulators with fat-containing food.
Beyond that, ALYFTREK also offers a potentially transformative option for approximately 150 people with CF in the U.S. with one of 31 mutations that are now eligible for a CFTR modulator for the first time.
“ALYFTREK is our fifth CFTR modulator to secure FDA approval and represents another significant milestone in our journey to serially innovate and to improve the lives of people living with cystic fibrosis,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “Our north star for more than 20 years has been to address the underlying cause of cystic fibrosis, treat more people with this disease, and bring more people to normal levels of CFTR function — ALYFTREK, with once-daily dosing, efficacy in 31 additional mutations.”
