Vertex Showcases Robust Clinical Data Supporting ALYFTREK® and the Critical Role of Sweat Chloride Reduction at 2025 European Cystic Fibrosis Conference
New findings reinforce the value of CFTR modulation and the potential of ALYFTREK to enhance health outcomes and quality of life in cystic fibrosis patients
Vertex Pharmaceuticals Incorporated, a global biotechnology leader in cystic fibrosis (CF) research and treatment innovation, presented a comprehensive body of new data at the 48th European Cystic Fibrosis Conference (ECFS), held from June 4 to June 7, 2025, in Milan, Italy. The data underscored the significant clinical benefits associated with cystic fibrosis transmembrane conductance regulator (CFTR) modulators—particularly its next-generation triple therapy, ALYFTREK® (vanzacaftor/tezacaftor/deutivacaftor).
The studies shared at ECFS 2025 encompassed a broad range of clinical outcomes, including pulmonary function, exacerbation frequency, nutritional metrics, and health-related quality of life. These results build on the growing body of evidence supporting the central role of sweat chloride (SwCl) reduction as both a biomarker and a therapeutic goal in CF treatment.
ALYFTREK: A Promising Advancement in CFTR Modulation
ALYFTREK, a once-daily oral regimen combining vanzacaftor, tezacaftor, and deutivacaftor, is Vertex’s latest innovation in CFTR modulation. It is currently approved for use in the United States and the United Kingdom for eligible patients with CF who possess at least one F508del mutation—the most common CF-causing genetic variant. Regulatory review is ongoing in several additional markets, including the European Union, Canada, Australia, New Zealand, and Switzerland.
At ECFS, Vertex unveiled new results from a pooled analysis that examined the relationship between sweat chloride levels and clinical outcomes across multiple CFTR modulator therapies, including ALYFTREK. Sweat chloride, a well-established biomarker of CFTR function, is used to evaluate how effectively a therapy restores chloride transport across epithelial cells in CF patients. Elevated sweat chloride levels are a hallmark of CF pathology, reflecting the dysfunction of the CFTR protein.
The pooled data analysis demonstrated a clear and consistent trend: as sweat chloride levels decreased—especially below the 60 mmol/L threshold—patients experienced notable improvements across a range of health outcomes. These included enhanced and sustained lung function, fewer pulmonary exacerbations, improved nutritional status, and better reported quality of life. Importantly, patients with sweat chloride levels below 30 mmol/L often saw the greatest numerical improvements, although some statistical overlap occurred with the group whose sweat chloride levels were between 30 and 60 mmol/L.
Quality of Life and Pediatric Benefits: Insights from Phase 3 Trials
In addition to the pooled sweat chloride analysis, Vertex presented a post hoc evaluation of Phase 3 trials focused specifically on ALYFTREK’s impact on patient-reported outcomes. These included randomized, controlled, and open-label studies in both adolescent and adult populations, as well as in children aged 6 to 11 years. The analysis offered compelling evidence that ALYFTREK not only improved clinical metrics but also delivered meaningful enhancements in patients’ day-to-day experiences with the disease.
Adolescents and adults receiving ALYFTREK reported statistically significant gains in health-related quality of life scores compared to those treated with the company’s earlier triple-combination therapy, TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor). These improvements spanned multiple domains, including respiratory symptoms, energy levels, emotional well-being, and physical functioning.
In the pediatric cohort, children aged 6-11 treated with ALYFTREK also demonstrated significant improvements in symptom burden and general functioning relative to those who received TRIKAFTA. These findings are particularly noteworthy, as they suggest that early initiation of highly effective CFTR modulation may not only slow disease progression but also allow children to experience a more normalized childhood free from many of the burdens typically associated with CF.
Expert Perspectives on Clinical Impact
Speaking on the significance of the newly presented data, Professor Isabelle Fajac, a leading pulmonologist and Professor of Physiology at APHP-Université Paris Cité in France, emphasized the importance of sweat chloride as a surrogate endpoint in CF therapy.
“These new data further demonstrate that reducing sweat chloride via treatment with CFTR modulators drives improved CFTR function and may ultimately result in better outcomes for patients across a variety of measures,” said Professor Fajac. “Importantly, the data also indicate that ALYFTREK, which has been shown to deliver even greater reductions in sweat chloride than TRIKAFTA, may drive improved quality of life and other health-related outcomes above and beyond even what we’ve seen with CFTR modulators to date.”
Her remarks reflect growing consensus within the CF clinical community that therapies capable of restoring CFTR function to near-normal levels could fundamentally alter the disease’s trajectory for many patients, potentially preventing or delaying complications that typically develop over time.
A Broader Vision for Transforming CF Care
The data presented at ECFS 2025 further reinforce Vertex’s longstanding commitment to transforming the treatment landscape for people living with CF. With each new generation of CFTR modulator therapies, the company aims not only to extend life expectancy but also to improve patients’ lived experiences, allowing them to lead healthier, fuller lives.
The potential impact of ALYFTREK is particularly meaningful for patients who continue to experience residual disease burden despite treatment with earlier-generation modulators. By delivering enhanced CFTR correction and potentiation, ALYFTREK offers a more complete restoration of chloride transport and has the potential to set a new standard in CF management.
Moreover, these findings highlight the critical role that early, aggressive intervention can play in preserving lung function, preventing nutritional decline, and safeguarding long-term health in individuals with CF—especially when treatment begins during childhood.
Global Access and Regulatory Progress
With approvals already secured in the U.S. and U.K., Vertex is working closely with regulatory authorities in multiple countries to expand access to ALYFTREK. As the therapy moves through the regulatory process in Europe and other regions, the company remains committed to ensuring that eligible patients worldwide can benefit from this innovation.
Ongoing real-world evidence collection, long-term extension studies, and registry-based outcomes research will continue to shape understanding of how ALYFTREK performs outside of clinical trial settings and how best to tailor CF treatment strategies to individual patient needs.
The data presented at the 2025 European Cystic Fibrosis Conference underscore a critical evolution in CF care—one where measurable improvements in CFTR function, as indicated by reductions in sweat chloride, are increasingly linked to tangible clinical and quality-of-life benefits. ALYFTREK stands at the forefront of this evolution, offering new hope for patients and families who have long awaited more effective therapies.
As Vertex continues to advance its mission to eliminate the burden of CF, these findings represent a major milestone—one that affirms the power of precision therapy and the promise of science to transform lives.
