Vertex Highlights Promising ALYFTREK and TRIKAFTA Data in Young Children with Cystic Fibrosis at European Conference
Vertex Pharmaceuticals has unveiled new clinical data demonstrating the potential of its next-generation cystic fibrosis (CF) therapies to further improve outcomes in young children living with the disease. Presented at the European Cystic Fibrosis Conference, the findings highlight encouraging results for ALYFTREK® (vanzacaftor/tezacaftor/deutivacaftor) in children aged 2 to 5 years and for TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor) in children aged 1 to under 2 years.
The data reinforce Vertex’s long-term strategy of restoring cystic fibrosis transmembrane conductance regulator (CFTR) function as early as possible in life, with the goal of altering disease progression and improving long-term health outcomes.
ALYFTREK Shows Significant CFTR Function Improvement in Children Ages 2–5
One of the key presentations focused on a Phase 3 open-label study evaluating ALYFTREK in children aged 2 to 5 years who have CFTR-responsive genotypes, including those carrying two copies of the F508del mutation (F/F) and those with one F508del mutation and one minimal function mutation (F/MF).
The 24-week study enrolled 67 children, all of whom completed treatment. Investigators reported that ALYFTREK was generally safe and well tolerated, with findings consistent with the therapy’s established safety profile observed in older populations.
The primary objective of the study was to evaluate safety and tolerability. However, researchers also assessed changes in sweat chloride levels, an important biomarker of CFTR function. Lower sweat chloride concentrations indicate improved CFTR activity and are associated with better disease control.
Results showed that children treated with ALYFTREK experienced a mean reduction of 9.6 mmol/L in sweat chloride levels compared with their baseline measurements while receiving TRIKAFTA. The improvement was observed rapidly and sustained throughout the 24-week treatment period.
Notably, 92% of participants achieved sweat chloride levels below 60 mmol/L, the diagnostic threshold commonly used for cystic fibrosis. Even more significant, 65% of children reached sweat chloride values below 30 mmol/L, a level associated with normal CFTR function seen in healthy carriers of CF mutations.
According to Vertex, these reductions in sweat chloride exceeded those observed with previous CFTR modulators in this age group, suggesting that ALYFTREK may offer enhanced restoration of CFTR activity.
Long-Term ALYFTREK Data Support Durable Benefits
In addition to the pediatric Phase 3 study, Vertex presented interim findings from two ongoing open-label extension studies evaluating the long-term safety and effectiveness of ALYFTREK.
The studies include children aged 6 years and older as well as adolescents and adults aged 12 years and above. Interim analyses covering 96 weeks of treatment demonstrated sustained efficacy and a favorable safety profile over nearly two years of follow-up.
The long-term data add to growing evidence supporting ALYFTREK as a potentially important advancement in CF care. Researchers reported continued clinical benefits alongside safety outcomes that remained consistent with previously established experience.
These findings are particularly important given the lifelong nature of cystic fibrosis treatment and the need for therapies that can maintain effectiveness over extended periods.
Experts Emphasize Importance of Early Intervention
Vertex executives and clinical investigators highlighted the significance of achieving greater restoration of CFTR function during early childhood, when irreversible organ damage may still be preventable.
Dr. Carmen Bozic, Executive Vice President of Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex, said the latest findings represent a major milestone in the company’s decades-long effort to transform cystic fibrosis care.
She noted that ALYFTREK is the first therapy shown to bring a majority of children between the ages of 2 and 11 years below the 30 mmol/L sweat chloride threshold. Because this level is comparable to values seen in healthy carriers of CF mutations, it serves as an important marker of near-normal CFTR function.
Professor Marcus A. Mall of Charité Universitätsmedizin Berlin, whose center participated in the clinical development program, emphasized that the data provide additional support for initiating highly effective CFTR modulation as early as possible.
According to Mall, improvements in sweat chloride have been accompanied by positive effects on other important indicators of disease activity, including measures of pancreatic function. He noted that the findings contribute to a growing body of evidence suggesting that early restoration of CFTR activity may help preserve organ function and improve long-term outcomes.
TRIKAFTA Demonstrates Strong Results in Infants and Toddlers
Vertex also presented results from a Phase 3 open-label study evaluating TRIKAFTA in children aged 12 months to under 24 months.
The study enrolled 54 participants and assessed treatment over a 24-week period. Similar to the ALYFTREK study, the primary endpoint focused on safety and tolerability.
Researchers reported that TRIKAFTA was generally safe and well tolerated in this very young population, with no new safety concerns identified. The observed safety profile was consistent with previous studies conducted in older pediatric and adult patients.
Importantly, treatment resulted in substantial improvements in CFTR function. Children receiving TRIKAFTA experienced a mean reduction in sweat chloride levels of 71.8 mmol/L from baseline, representing a statistically significant and clinically meaningful improvement.
Nearly all participants—98%—achieved sweat chloride levels below the diagnostic threshold of 60 mmol/L, while 68.6% reached values below 30 mmol/L.
These findings suggest that initiating highly effective CFTR modulator therapy during infancy may offer a powerful opportunity to address the underlying cause of cystic fibrosis before significant disease progression occurs.
Regulatory Plans Moving Forward
Based on the positive findings, Vertex plans to pursue expanded regulatory approvals for both therapies.
The company intends to submit global regulatory applications for ALYFTREK in children aged 2 to 5 years during the first half of 2026. If approved, the therapy could become available to younger patients who carry eligible CFTR mutations.
For TRIKAFTA, Vertex has already initiated global regulatory submissions seeking approval for use in children aged 1 to under 2 years.
At present, ALYFTREK remains approved for patients aged 6 years and older, while TRIKAFTA is approved for patients aged 2 years and older who have eligible CFTR mutations. Use in younger children remains investigational pending regulatory review.
Safety Remains a Key Focus
Vertex continues to emphasize the importance of monitoring safety during treatment with both ALYFTREK and TRIKAFTA.
Both medicines carry warnings related to potential liver injury, including rare but serious cases of liver failure reported with CFTR modulator therapies. Healthcare providers are advised to perform routine liver function monitoring before and during treatment.
Additional precautions include monitoring for hypersensitivity reactions, neuropsychiatric symptoms, intracranial hypertension, potential drug interactions involving CYP3A inhibitors and inducers, and eye examinations in pediatric patients because of the risk of cataracts.
The most commonly reported adverse events with ALYFTREK include cough, upper respiratory tract infections, headache, fatigue, elevated liver enzymes, rash, and sinus congestion. Common adverse reactions associated with TRIKAFTA include headache, respiratory infections, abdominal pain, diarrhea, rash, and elevated liver function markers.
Advancing Toward Earlier Disease Modification
The latest clinical findings underscore the growing potential of highly effective CFTR modulators to change the treatment landscape for cystic fibrosis. By initiating therapy during infancy and early childhood, clinicians may be able to preserve organ function, delay or prevent complications, and improve quality of life over the long term.
As Vertex advances regulatory submissions for younger age groups, the company continues to move closer to its goal of making transformative CFTR-modulating therapies available across the broadest possible range of patients living with cystic fibrosis.
The newly presented data suggest that both ALYFTREK and TRIKAFTA may play an increasingly important role in early intervention strategies aimed at addressing the root cause of cystic fibrosis and potentially reshaping the future of care for children diagnosed with the disease.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including IgA nephropathy, neuropathic pain, APOL1-mediated kidney disease, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, generalized myasthenia gravis, and myotonic dystrophy
