FDA approves Alyftrek once-daily oral combination for cystic fibrosis

The US Food and Drug Administration has approved Alyftrek, a once-daily oral combination of vanzacaftor, tezacaftor, and deutivacaftor, for the treatment of cystic fibrosis (CF) in adults and children aged 6 and older, Vertex Pharmaceuticals announced on Friday.

“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, and lower sweat chloride levels than TRIKAFTA, is another step in achieving this goal.”

This approval is based on the most comprehensive Phase 3 pivotal program ever conducted in CF, including more than 1,000 patients across more than 20 countries and more than 200 sites. These data were previously released at the conclusion of the studies and presented at the North American Cystic Fibrosis Conference in September of this year. The Phase 3 studies in people with CF ages 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 (including absolute change from baseline in sweat chloride [SwCl] compared to TRIKAFTA). In the Phase 3 study of children with CF ages 6-11 years, ALYFTREK demonstrated safety, the primary endpoint. Secondary endpoints, such as absolute change from baseline in ppFEV1 and absolute change from baseline in SwCl, were presented, supporting the benefit of ALYFTREK in this age group. ALYFTREK was generally well tolerated across all studies.

“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.”

ALYFTREK is the first, once-daily CFTR modulator. In a recent survey, approximately 75% of physicians reported that more convenient dosing is a very high unmet need for people with CF. Specifically, people with CF will have the added benefit from a once-daily dosing regimen, given the need to take CFTR modulators with fat-containing food. ALYFTREK also offers a potentially transformative option for approximately 150 people with CF in the U.S. with one of 31 mutations who are now eligible for a CFTR modulator for the first time.

ALYFTREK was also submitted to global health authorities and is under regulatory review in the European Union, the United Kingdom, Canada, Switzerland, Australia and New Zealand.

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a 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. 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. The 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, this 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 is in the 30s, but with treatment, projected survival is improving.