Vertex Gains EU Approval for ALYFTREK®, a Next-Generation CFTR Modulator for Cystic Fibrosis Patients
Vertex Pharmaceuticals (Nasdaq: VRTX) announced today that the European Commission has granted marketing authorization for ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor), a new, once-daily triple-combination CFTR modulator therapy for the treatment of cystic fibrosis (CF) in individuals aged six years and older who possess at least one non-class I mutation in the CFTR gene. This approval marks a significant milestone in expanding treatment options for people with CF across the European Union (EU).
“This approval brings hope to thousands of people with CF throughout the EU,” said Dr. Reshma Kewalramani, Chief Executive Officer and President of Vertex. “ALYFTREK has demonstrated enhanced CFTR protein function compared to our previous triple-combination therapy, KAFTRIO®, and moves us closer to our overarching goal of normalizing CFTR activity in all people with CF.”
Clinical Trial Results Show Promising Advancements
The approval follows results from two pivotal, head-to-head Phase 3 clinical trials comparing ALYFTREK to KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor. These studies demonstrated that the new once-daily regimen was non-inferior in terms of absolute improvement in lung function as measured by percent predicted forced expiratory volume in one second (ppFEV1). In addition, ALYFTREK showed superior results in reducing sweat chloride levels, which is a direct biomarker of CFTR function.
Professor Marcus A. Mall, M.D., Chair of the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center at Charité Universitätsmedizin Berlin, emphasized the clinical significance of the approval. “CF care has been revolutionized by the advent of CFTR modulators,” he said. “ALYFTREK’s ability to further reduce sweat chloride concentrations suggests that it brings more patients closer to achieving near-normal CFTR function. This can potentially translate into better long-term outcomes and an improved quality of life.”
Expedited Access in Select European Countries
Thanks to existing reimbursement frameworks in countries such as Ireland and Denmark, as well as health system access provisions in Germany, patients in these regions will gain access to ALYFTREK soon after the European Commission’s approval. Vertex also confirmed it is actively working with health authorities and reimbursement bodies across other EU member states to ensure that eligible patients across Europe can receive timely access to the newly approved therapy.
Understanding Cystic Fibrosis and the Role of CFTR Modulators
Cystic fibrosis is a rare, inherited, and life-shortening genetic disorder that affects more than 109,000 people globally, including approximately 94,000 individuals across North America, Europe, and Australia. CF is caused by mutations in the CFTR gene, which impair or eliminate the function of the CFTR protein — a critical channel responsible for regulating salt and water transport across cell membranes in multiple organs, including the lungs, pancreas, and gastrointestinal tract.
The disease is characterized by thick, sticky mucus buildup in the lungs, leading to recurrent infections and progressive respiratory decline. The median age of death is in the 30s, though the outlook is improving with the development of effective therapies like CFTR modulators. Among those affected, the vast majority carry at least one F508del mutation, the most common CFTR gene variant.
Vertex has pioneered the development of CFTR modulators, which improve the function of the defective CFTR protein. The company’s current therapies treat over 75,000 people with CF in more than 60 countries, representing approximately two-thirds of all diagnosed individuals eligible for these medicines.
The Importance of Sweat Chloride Reduction
Sweat chloride concentration is an important diagnostic and prognostic marker for CF. Levels equal to or above 60 mmol/L typically indicate a CF diagnosis, while levels below 30 mmol/L are considered normal and are typically seen in individuals who are carriers of a CFTR mutation but do not have the disease.
Vertex’s long-term therapeutic goal has been to normalize CFTR function, and ALYFTREK represents a significant advancement toward this goal. The therapy’s ability to lower sweat chloride to near-normal levels (below 30 mmol/L) could signal the possibility of slower disease progression, fewer pulmonary exacerbations, and improved quality of life.
About ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor)
ALYFTREK combines three agents that target the underlying defect in CF at different stages:
- Vanzacaftor and tezacaftor are “correctors” that increase the amount of CFTR protein at the cell surface by assisting in the proper folding and trafficking of the protein.
- Deutivacaftor is a “potentiator” that enhances the opening of the CFTR channel, thereby improving the flow of salt and water across epithelial membranes.
The therapy is indicated in the EU for people aged 6 years and older who have at least one non-class I CFTR mutation.
ALYFTREK is currently approved in the United States, United Kingdom, and European Union, and is under regulatory review in Canada, Switzerland, Australia, and New Zealand.
For more detailed information, including safety and prescribing guidance, healthcare professionals are advised to consult the Summary of Product Characteristics (SmPC) available on the European Medicines Agency (EMA) website.
