Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex - LARVOL DELTA

Evaluating Sinonasal Airspace Changes Pre- and Post-Treatment with Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis (COSM 2025) - "Patients with CF treated with ETI exhibited a significant increase in sinonasal airway patency, as evidenced by volumetric quantification analysis of surface area and volume differences. These increases in both parameters showed strong significant correlations with Lund-Mackay scores; however, no such correlations were observed with patient reported subjective SNOT-22 scores."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Psychometric validity and subdomain analysis of the SNOT-22 in cystic fibrosis sinusitis (COSM 2025) - "Participant data from three studies investigating the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on CF-CRS were used for validity assessments...The SNOT-22 is a valid, reliable, and responsive instrument for evaluating CRS-specific QOL in PwCF, and functions effectively as a unidimensional construct across most of its 22 items. Our findings suggest a SNOT-22 factor structure in PwCF similar to existing domain structures in non-CF populations."

Cystic Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Biological and clinical effects of significantly corrected CFTR function in infants and young children with cystic fibrosis: The BEGIN study (PAS 2025) - "Background: The approval of elexacaftor/tezacaftor/ivacaftor (ETI) in people with CF with ≥1 F508del mutation provides an opportunity to understand pulmonary and non-pulmonary effects of highly effective modulator therapy (HEMT: ivacaftor or ETI)... Thirty-four US centers have enrolled 115 participants in Part A with an average follow-up of 1.7 years and mean±SD age at enrollment 2.9±1.4 years. Part B has enrolled 192 children who started HEMT (87/192 from Part A and 105 new participants) of which 160 have completed the 6 month visit. Age at enrollment into Part B was 4.2±1.4 years."

Clinical • Cystic Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Immunology • Respiratory Diseases

Cholesterol and triglyceride concentrations following 12-18 months of clinically prescribed elexacaftor-tezacaftor-ivacaftor-PROMISE sub-study. (PubMed, J Clin Transl Endocrinol) - "In a population of youth and young adults with CF, TC and HDL-C were higher after 12-18 months of ETI, but differences in TC were attenuated with adjustment for BMI-Z. Prevalence of low HDL-C was high at both timepoints."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • Myocardial Infarction

Quantification of Ivacaftor, Tezacaftor, Elexacaftor, and Lumacaftor and their active metabolites in plasma using UHPLC-MS/MS: Doors open to the application of therapeutic drug monitoring in cystic fibrosis treatment. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "All seven components were stable in EDTA plasma for ten days in the autosampler after sample preparation and through four freeze-thaw cycles. The developed assay was applied in routine TDM analysis to investigate exposure to elexacaftor, tezacaftor, ivacaftor and their metabolites in people with CF undergoing treatment with Kaftrio®."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Succinate Chemosensing Induces CFTR-dependent Airway Clearance Which Is Impaired in Cystic Fibrosis. (PubMed, Am J Respir Cell Mol Biol) - "Moreover, when HBECs derived from ΔF508-CF individuals lacked succinate-induced anion secretion, unless incubated with elexacaftor-tezacaftor-ivacaftor (ETI), which restored succinate-induced anion secretion, confirming the tight relationship between SUCNR1 signalling and CFTR function. We have identified a novel mechanism for regulating CFTR/MCC activation which is defective in CF airways. We propose that succinate acts as a danger molecule that alerts the airways to the presence of pathogens leading to a flushing out of the airways."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • CFTR • SUCNR1

How Effectively Can Oxidative Stress and Inflammation Be Reversed When CFTR Function Is Pharmacologically Improved? (PubMed, Antioxidants (Basel)) - "The triple therapy with elexacaftor-tezacaftor-ivacaftor (ETI) suggests that CFTR activity in individuals with at least one F508del mutation can be partially restored to about 50% of normal levels...By analyzing changes in gene expression, epigenetic modifications, protein profiles and metabolic processes in airway-derived samples, it could be possible to uncover the mechanisms driving persistent oxidative stress and inflammation. These insights could pave the way for identifying new therapeutic targets to fully restore airway health and overall physiological balance."

Journal • Review • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Real-Life in Cystic Fibrosis Pediatric Patients Treated With Kaftrio: A Descriptive Observational Study. (PubMed, Clin Pediatr (Phila)) - "A transient increase in cough and secretions was noted in 61.53% after starting treatment. Kaftrio improves lung function and BMI and also reduces respiratory exacerbations and sweat chloride levels."

Journal • Observational data • Cough • Cystic Fibrosis • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases

Tracheal Diverticula in People with Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor: An Italian Multicenter Retrospective Study. (PubMed, J Clin Med) - " TD may be identified in chest CT obtained in pwCF in treatment with ETI. Further studies and a longer follow up are needed to confirm these findings."

Journal • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Relationship between theratyping in nasal epithelial cells and clinical outcomes in people with cystic fibrosis. (PubMed, Eur Respir J) - "We identified thresholds of nasal epithelial cell theratype response in pwCF to predict clinical benefit from CFTR modulator therapy. The utility of this therapy testing platform to predict a clinical response improves when multiple clinical outcome measures are combined."

Clinical data • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for F508del and a minimal function mutation: Results from a 96-week open-label extension study. (PubMed, Eur Respir J) - P3 | "ELX/TEZ/IVA treatment was generally safe and well-tolerated, with a safety profile consistent with parent study and older age groups. After starting ELX/TEZ/IVA, children had robust improvements in sweat chloride concentration and lung function that were maintained through 96 weeks. These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in this pediatric population. (Clinical Trials.gov, NCT04545515; EudraCT, 2020-001404-42)."

Journal • Cough • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pain • Pediatrics • Pulmonary Disease • Respiratory Diseases

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Extension Study. (PubMed, Am J Respir Crit Care Med) - P3 | "During this 192-week open label extension study, the longest clinical study of a CFTR modulator to date, ELX/TEZ/IVA remained generally safe and well-tolerated. Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates, and nutritional status. The estimated annualized rate of change in ppFEV1 suggests no evidence of pulmonary function loss across the study population over the 4-year treatment period. These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF. Clinical trial registration available at www."

Journal • P3 data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Elexacaftor-Tezacaftor-Ivacaftor Era and cystic fibrosis liver disease progression: a 10-year national study (EASL 2025) - No abstract available

Cystic Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Respiratory Diseases

The impact of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the pulmonary microbiota. (PubMed, Microbiology (Reading)) - "The approved triple therapy of elexacaftor, tezacaftor and ivacaftor (ETI), commercially known as Trikafta, increases CFTR channel function, leading to improvements in sweat chloride concentration, exercise capacity, body mass index, lung function and chronic respiratory symptoms...However, colonization with the common CF respiratory pathogens persists and remains a major cause of morbidity and mortality. Here, we review the current literature on the effect of ETI on the respiratory microbiota and discuss the challenges in addressing CF lung infections in the era of these new life-extending therapies."

Journal • Review • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • CFTR

Navigating ETI Use in Pediatric Patient with CF Post Lung Transplant (ISHLT 2025) - "Introduction Evidence is growing for the use of elexacaftor/tezacaftor/ivacaftor (ETI) in cystic fibrosis (CF) patients post lung transplant for extrapulmonary benefits...Early growth of Blastobotrys and Aspergillus niger post-transplant prompted ongoing use of isavuconazole...Variability in ETI levels was seen irrespective of dose increases, and modified dosing may not be needed for all patients on azole therapy. This case highlights the importance of individualized monitoring and dosing adjustments in CF lung transplant patients on ETI."

Clinical • Constipation • Cough • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Otorhinolaryngology • Pediatrics • Pulmonary Disease • Respiratory Diseases • Sinusitis • Transplant Rejection • Transplantation • CYP3A4

Adenine base editing of CFTR using receptor targeted nanoparticles restores function to G542X cystic fibrosis airway epithelial cells. (PubMed, Cell Mol Life Sci) - "52% editing alone or 17% and 52% editing of CFTR G542X plus treatment with CFTR modulators (VX-445/VX-661/VX-770; ETI/Trikafta/Kaftrio) increased epithelial CFTR protein expression, CFTR protein band C abundance, CFTR172 inhibitable anion transport, and changes in airway surface liquid height and pH in response to vasoactive intestinal peptide (VIP) stimulation. Epithelial scratch repair speed and directionality was also improved. These data provide proof-of-concept that ABE of G542X to G542R in human CF airway epithelial cells could provide a feasible therapy for this variant."

Journal • Cystic Fibrosis • Developmental Disorders • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • BMI1 • CFTR

European Commission Approves Expanded Label for KAFTRIO in Combination With Ivacaftor for People With Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals...today announced that the European Commission has granted regulatory approval for a label expansion of KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with ivacaftor for the treatment of people with cystic fibrosis (CF). With this approval, the indication has been expanded to include all patients ages 2 years and older who have at least one non-class I mutation in the cystic fibrosis conductance regulator (CFTR) gene....As a result of existing KAFTRIO reimbursement agreements in Austria, Denmark, Ireland, Norway and Sweden, and provisions for access in health care systems such as Germany, eligible patients in these countries will have access to the expanded indication of the therapy shortly....Vertex will continue to work collaboratively with reimbursement authorities across the European Union to ensure access for all eligible patients, as quickly as possible."

EMA approval • Reimbursement • Cystic Fibrosis

Improved Clinical Outcomes With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease: Real-World Evidence From an Italian Single-Center Study. (PubMed, Pharmacol Res Perspect) - "Overall, lung function, SwCl, PEx rate, CFQ-R scores and BMI improved after 24 months of ETI treatment. ETI was well tolerated, and none of the patients interrupted the treatment due to toxicity."

Clinical data • HEOR • Journal • Real-world evidence • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

Effects of an Exercise Intervention on Exercise Capacity in Adults With Cystic Fibrosis: A Quasi-Experimental Study Comparing Individuals Treated With and Without Elexacaftor/Tezacaftor/Ivacaftor. (PubMed, Pediatr Pulmonol) - "Independent of ETI treatment, adult pwCF improve their exercise capacity by participating in a regular exercise program. ETI treatment appears to enhance time spent in higher PA intensities. Despite the effectiveness of CFTR modulators, regular PA and exercise remain essential to maintain and improve exercise capacity in pwCF."

Clinical • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Cystic fibrosis: new challenges and perspectives beyond elexacaftor/tezacaftor/ivacaftor. (PubMed, Ther Adv Respir Dis) - "Moreover, a significant number of pwCF are unresponsive to these drugs or cannot afford their high costs. We, therefore, discussed health inequity issues and alternative therapeutic strategies under development aiming to obtain effective therapies for all pwCF."

Journal • Review • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Understanding beliefs about elexacaftor-tezacaftor-ivacaftor therapy in adults living with cystic fibrosis. (PubMed, BMJ Open Respir Res) - "Patients reported strong beliefs in the necessity of ETI therapy. Although concerns were lower, a significant proportion of the sample had strong concerns about their ETI therapy. By being aware of people with CF's necessity and concerns beliefs around ETI therapy clinical teams will be better armed to engage them in treatment decisions and support optimal adherence."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A unique combination of heterozygous CFTR gene variants in a person with cystic fibrosis and M. abscessus infection. (PubMed, Respiration) - "This case highlights a unique combination of heterozygous CFTR variants in a person with late-onset CF respiratory disease, which may be amenable to CFTR modulation therapy."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • CFTR

Olfaction, Eating Preference, and Quality of Life in Cystic Fibrosis Chronic Rhinosinusitis. (PubMed, Laryngoscope) - P | "In PwCF, OD was associated with increased CRS severity, impaired olfactory QOL, and decreased CFQ-R eating. There were no differences in SIT-40 or QOD-NS scores based on HEMT status."

HEOR • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis

Clearance of Mycobacterium abscessus with elexacaftor/tezacaftor/ivacaftor in a patient with cystic fibrosis (ESCMID Global 2025) - No abstract available

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Airway epithelial air-liquid-interface culture systems for high-resolution investigations of bacterial infection dynamics during treatment with elexacaftor/tezacaftor/ivacaftor (ESCMID Global 2025) - No abstract available

Infectious Disease