Vertex reports increased fecal elastase levels and reduced pancreatic enzyme replacement therapy use in young children with cystic fibrosis treated with ALYFTREK.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Vertex Pharmaceuticals reported interim findings suggesting improved pancreatic function in some children aged 2–5 years with cystic fibrosis (CF) treated with ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor). Presented as a late-breaking poster at the North American Cystic Fibrosis Conference (NACFC), the findings showed increased fecal elastase-1 levels and discontinuation of pancreatic enzyme replacement therapy (PERT) in some children. However, the results are preliminary, and their long-term clinical significance remains uncertain.
What Did the Interim Data Show?
The findings came from Cohort 2 of Study VX22-121-106, an ongoing open-label extension study evaluating ALYFTREK in children aged 2–5 years. The interim analysis included children who had received at least 48 weeks of treatment.
Among the 48 children eligible for the pancreatic enzyme replacement therapy “(PERT)-discontinuation sub-study”, the key findings were:
- Mean fecal elastase-1 (FE-1): 239.7 μg/g, representing a mean increase of 110.2 μg/g from baseline.
- Pancreatic sufficiency threshold: 48.6% of children reached FE-1 levels of at least 200 μg/g, the threshold used to indicate pancreatic sufficiency.
- PERT discontinuation: 18 of 48 children (37.5%) discontinued PERT during the sub-study.
- Duration without PERT: The mean duration was 8.6 weeks, ranging from 1.9 to 17.6 weeks.
- Earlier PERT discontinuation: Seven additional participants had discontinued PERT before becoming eligible for the sub-study.
- Overall PERT use: Across the full cohort of 66 children, 50% were not receiving PERT at the interim data cut-off.
These findings suggest that exocrine pancreatic function may improve in some young children receiving ALYFTREK. However, the results are preliminary, and the relatively short period without PERT limits conclusions about the durability of these changes. Increased FE-1 levels and PERT discontinuation do not, by themselves, establish complete pancreatic recovery or demonstrate sustained improvements in nutritional status and long-term clinical outcomes.
Why Are These Findings Important?
CF is a genetic condition caused by variants in the CFTR gene that disrupt the movement of salt and water across cell surfaces. In many children, the disease impairs pancreatic function, reducing the digestive enzymes needed for nutrient absorption. PERT replaces these enzymes and helps the body digest food.
Pancreatic exocrine insufficiency is a common complication of CF and can contribute to nutritional deficiencies and impaired growth. Treatment with CFTR modulators targets the underlying protein dysfunction, potentially affecting disease manifestations beyond the lungs.
The increase in FE-1 levels and discontinuation of PERT in some participants suggest that exocrine pancreatic function may improve during treatment with ALYFTREK. These findings are notable because pancreatic insufficiency associated with CF has traditionally been considered difficult to reverse.
However, increased FE-1 levels do not, by themselves, establish complete pancreatic recovery or demonstrate sustained improvements in growth, nutritional status or long-term health outcomes. The findings therefore represent an encouraging signal rather than definitive evidence of lasting clinical benefit.
What Are the Limitations?
The study is ongoing and open-label, and the reported findings are from an interim analysis. The company announcement does not describe a concurrent control group for these results, limiting comparisons with alternative treatments or no treatment. Consequently, the findings cannot establish the extent to which ALYFTREK caused the observed changes or predict which children are most likely to benefit.
The duration without PERT was also relatively short, averaging 8.6 weeks among the 18 children who discontinued treatment during the sub-study. Longer follow-up is needed to determine whether pancreatic function remains improved, whether children can safely remain off enzyme replacement, and whether these changes translate into sustained nutritional and clinical benefits.
PERT should not be reduced or discontinued solely on the basis of these interim findings. Any treatment changes must be guided by the child’s specialist team, with appropriate clinical and nutritional monitoring.
Regulatory Status and Future Implications
In the United States, ALYFTREK is approved for adults and children aged six years and older with a clinical diagnosis of CF and at least one CFTR variant that is responsive to treatment based on clinical and/or in vitro data, or that results in CFTR protein production.
Its use in children aged 2–5 years remains investigational. The reported findings do not extend the drug’s approved indication to this younger age group.
Further follow-up should clarify the durability of the observed pancreatic-function changes, identify which children are most likely to benefit, and determine whether improvements in FE-1 and reduced PERT use translate into lasting nutritional and clinical outcomes.
For now, the findings suggest that early treatment with ALYFTREK may improve pancreatic function in some young children with CF. However, the available interim data do not establish that pancreatic insufficiency can be reversed in all children or that the benefits will persist over the long term.
Reference
Vertex Pharmaceuticals. Vertex to Present New Data on ALYFTREK® at the North American Cystic Fibrosis Conference. October 9, 2026.
Evaluation of Long-Term Safety and Efficacy of Vanzacaftor/Tezacaftor/Deutivacaftor in Cystic Fibrosis Participants 1 Year of Age and Older, ClinicalTrials.gov ID NCT05844449
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.