Symdeko (tezacaftor/ivacaftor) / Vertex - LARVOL DELTA

Changes in Inhaled Antibiotic Associated lung function outcomes in the CFTR-Modulator Era. (PubMed, Chest) - "The risk of treatment emergent infections was highest in Pa negative pwCF who conversely did not have antibiotic-associated benefit on lung function. For pwCF with chronic Pa the antibiotic-associated benefit decreased as CFTR-modulator use increased."

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

In Vitro Responsiveness of 417 CFTR Variants to Vanzacaftor/Tezacaftor/Ivacaftor. (PubMed, J Cyst Fibros) - "We evaluated 417 CFTR variants for VTI responsiveness, including 272 tested for the first time and 145 previously categorized as non-responsive (NR) or borderline-responsive (BR) to ETI. Overall, ∼76% of variants achieved ≥10% of WT improvement, the threshold for responsiveness. This included 87% of newly tested variants and 55% of ETI NR/BR variants. Notably, 50 variants classified as NR/BR to ETI reached the responsive threshold with VTI using empirical Bayes criteria. Compared with ETI, VTI demonstrated broader efficacy across this dataset. These results expand the number of CFTR variants likely to benefit from highly effective modulator therapy and highlight remaining variants that may require alternative therapeutic strategies."

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

Association of dental diseases with pulmonary outcomes in a multicenter cohort of adolescents and young adults with CF. (PubMed, J Cyst Fibros) - "Among 203 participants (mean (SD) age at enrollment of 18.7 (5.0) years, 86% on elexacftor-tezacaftor-ivacaftor or ivacaftor)), we found that ≥3 surfaces with untreated caries was associated with a mean decrement of -0.88 (95% CI -1.61, -0.16, p = 0.02) in FEV1 z score compared to no untreated caries, and a mean decrement of -11.7 (95% CI -20.7, -2.7, p = 0.01) in the CFQ-R respiratory domain. We did not observe an association between gingivitis and respiratory outcomes. Our results suggest that poor oral health could be a modifiable risk factor for worse lung health in CF, and that prevention and treatment of dental caries could potentially improve respiratory health in adolescents and young adults with CF, even in the post-modulator era."

Journal • Dental Disorders • Respiratory Diseases

PANCREATIC FUNCTION RESPONSE TO EARLY CFTR MODULATOR TREATMENT IN CYSTIC FIBROSIS PATIENTS (ESPGHAN 2026) - "Methods A retrospective descriptive study was conducted on CF patients with elaxacaftor-tezacaftor-ivacaftor (ETI) therapy.Two groups were compared:those who received ETI between 2-6 years versus those >6years.Demographic data, mutations and FE were collected.Data were analyzed using descriptive statistics and Student's t-test...These results support early treatment with CFTR modulators in CF pediatric population. Contact e-mail address [email protected]"

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

Real-World Clinical Outcomes of Lumacaftor-Ivacaftor or Tezacaftor-Ivacaftor Therapy in Children With Cystic Fibrosis Homozygous for Phe508del. (PubMed, Pediatr Pulmonol) - "This real-world study demonstrates that dual CFTR modulators in children homozygous for Phe508del result in a significant reduction in SCC and modest improvements in ppFEV1. These findings support the efficacy and safety of dual modulator therapy in pediatric CF care."

Clinical data • Journal • Real-world evidence • Cystic Fibrosis • Genetic Disorders • Immunology • Ophthalmology • Pediatrics • Pulmonary Disease • Respiratory Diseases • CFTR

Clinical, functional and therapeutic evaluation of CFTR variant I507del. (PubMed, J Cyst Fibros) - "In primary human nasal epithelial (HNE) cultures from two donors carrying I507del and a null variant (2184delA or 621+1G>T), baseline CFTR activity was <1% of wild-type (WT) (0.11-0.16 µA/cm²) and elexacaftor-tezacaftor-ivacaftor (ETI) failed to increase function...Vanzacaftor/tezacaftor/ivacaftor (VTI) reproducibly restored ∼6.4% WT (1.14 ± 0.4 µA/cm²) activity in donor-derived HNEs and produced mature CFTR protein in Flp-In-CFBE models...The robust RNA-function relationship highlights RNA amplification strategies as potential adjuncts to increase rescue. These findings identify I507del as an ETI-refractory allele with minimal responsiveness to VTI suggesting careful consideration before embarking upon modulator treatment of individuals with CF carrying this variant."

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

Global Research Status and Trends in Quality of Life in Children With Cystic Fibrosis From 1985 to 2025: A 40-Year Bibliometric Analysis. (PubMed, Pediatr Pulmonol) - "The present study offers a global overview to researchers into quality of life in children with cystic fibrosis and also to healthcare professionals in clinical practice. It gives insights for future research on the topic and also shows existing gaps that could guide future studies in the field."

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

Personalized Theratyping Trial (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: George Solomon | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Real-world safety of Symdeko: insights from the food and drug administration adverse event reporting system. (PubMed, Front Med (Lausanne)) - "These findings underscore the importance of ongoing monitoring and management for patients treated with Symdeko. Future larger-scale prospective studies are necessary to validate these findings and enhance patient management strategies."

Adverse events • Journal • Real-world evidence • CNS Disorders • Cystic Fibrosis • Depression • Genetic Disorders • Immunology • Infectious Disease • Mood Disorders • Nephrology • Pain • Psychiatry • Pulmonary Disease • Renal Calculi • Respiratory Diseases • Suicidal Ideation • CFTR

Long term causal effects of ivacaftor on airway microbiology and lung function outcomes in people with CF: An emulation of target trials with the U.S. CF Foundation Patient Registry data (NACFC 2025) - "The per-protocol analysis censored individuals who deviated from their initial treatment, and a third approach further censored those who started other modulators (lumacaftor/ivacaftor or tezacaftor/ivacaftor). Our findings demonstrate a robust long-term clinical benefit over a 7-year period of ivacaftor across both clinical and microbiological outcomes, particularly among younger patients and those with gating mutations. These results provide real-world support for sustained ivacaftor use in eligible CF populations."

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

Theratyping of 400 CF-associated variants in FRT cells to assess variant responsiveness to triple combination CFTR modulator vanzacaftor/ tezacaftor/ivacaftor (VNZ/TEZ/IVA) (NACFC 2025) - "We recently published findings from a large-scale theratyping study, evaluating 655 CFTR variants, including 478 variants without FDA approval at the time, for their responsiveness to elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the active ingredients of Trikafta® [1]...A clinical investigation of the new Vertex triple combination (ALYFTREK®)i... We demonstrated significant rescue efficacy of VNZ/TEZ/IVA for a high percentage of CFTR variants currently not on the label for approved HEMT, indicating that confirmatory studies by Vertex would be valuable for future label expansions. VNZ/TEZ/IVA treatment may provide a therapeutically meaningful approach for several variants that did not positively respond to ELX/TEZ/IVA."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Real-life effect of lumacaftor-ivacaftor or tezacaftor-ivacaftor in children with Phe508del CFTR mutation (ERS 2025) - "The therapy was well tolerated. This study shows that CFTR modulator therapy in children with Phe508del leads to reduced SSC and modest improvements in lung function, supporting the efficacy and safety of these treatments in clinical practice."

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

Single-Nuclei RNA Sequencing reveals nasal epithelial changes in CF patients treated with ELE/TEZ/IVA (ERS 2025) - "Rationale: The combination of tezacaftor, elexacaftor, and ivacaftor (ELE/TEZ/IVA) has demonstrated significant benefits in cystic fibrosis (CF) patients with specific mutations. Three months of ELE/TEZ/IVA treatment enhanced the proportion of basal cells (airway epithelial progenitors) and ionocytes (key CFTR-expressing cells) in clinically responsive patients. The observed reduction in interferon signaling suggests decreased viral susceptibility, highlighting the treatment's potential to restore epithelial homeostasis and improve clinical outcomes."

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

Personalized Dosing of ELE/TEZ/IVA in Cystic Fibrosis: integrating pharmacokinetics and pharmacogenetics for Improved Outcomes (ERS 2025) - "Rationale: Elexacaftor-tezacaftor-ivacaftor (ELE-TEZ-IVA) is effective for CF patients with ≥1 F508del mutation, but interindividual variability in response and adverse drug reactions (ADRs) necessitate better understanding of pharmacokinetics (PK) and pharmacogenetics (PG). A larger cohort is yet ongoing to clarify exposure-response relationships and genetic variability's role in ADRs, with emerging trends for specific molecules/metabolites."

Biomarker • PK/PD data • Cystic Fibrosis • Genetic Disorders • Immunology • Psychiatry • Respiratory Diseases • CYP3A4

Long-term non-pulmonary outcomes of Elaxacaftor-Tezacaftor-Ivacaftor (ETI) in pwCF (ERS 2025) - "ETI significantly and sustainably improved sweat chloride and BMI in all groups over a period of 2 yrs, whereas no significant changes were observed for prevalence of pancreatic enzymes or insulin and for incidence of DIOS."

Pulmonary Disease • Respiratory Diseases

Impact of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance and Abnormal Glucose Metabolism: A Phase 3b, Open-Label Clinical Trial. (PubMed, Am J Respir Crit Care Med) - P3b | "ELX/TEZ/IVA treatment led to clinically meaningful improvements in blood glucose regulation with significant within-group decreases in blood glucose levels following OGTT and improved dysglycemia categorization in people with CF with early IGT or CFRD. Clinical trial registration available at www."

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

Condition-dependent effects of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) on Aspergillus fumigatus growth. (PubMed, Microbiol Spectr) - "By contrast, during macrophage infection, we observed that high concentrations of ETI treatment promoted fungal growth but inhibited inflammasome activation.IMPORTANCEThe advent of ETI therapy represents a pivotal moment, signaling the onset of major changes in the medical field of cystic fibrosis and its related infectious diseases. However, the impact of ETI treatment on the patient's microbiota and pathogens has to be further studied as proof arises of changes in patient colonization."

Journal • Allergic Bronchopulmonary Aspergillosis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Indirect evaluation of lung condition by means of LF-NMR following chest physiotherapy or ETI administration in cystic-fibrosis patients. (PubMed, Heart Lung) - "This data strengthens the rationale for T2m employment in CF lung disease monitoring and show that T2m can be profitably used to complement the FEV1 test."

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

Pregnancy and neonatal outcome following in utero exposure to CFTR modulators: A multicentre prospective case series. (PubMed, J Cyst Fibros) - "This prospective case series - the largest to date - does not suggest a high rate of MCA or neonatal adverse outcomes in CFTRm-exposed pregnancies. Further studies including long-term follow-up of in utero exposed children are needed to confirm these findings."

Journal • Cataract • CNS Disorders • Cystic Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Ophthalmology • Pulmonary Disease • Respiratory Diseases

Real-world population pharmacokinetics of tezacaftor-ivacaftor in children with cystic fibrosis: The SYM-CF study. (PubMed, Br J Clin Pharmacol) - "This is the first study to investigate the popPK of tezacaftor-ivacaftor in cwCF. The established models can be used for more personalized dosing in children experiencing suboptimal efficacy, adverse effects, drug-drug interactions, or where adherence is a concern."

Journal • PK/PD data • Real-world evidence • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Effect of vanzacaftor/tezacaftor/ivacaftor on cystic fibrosis airway epithelial cells (ECFS 2025) - "Objectives: The latest triple-component CFTR modulator drug, consisting of vanzacaftor (V), tezacaftor (T) and deutivacaftor (D), is becoming a new treatment alternative to the established combination of elexacaftor (E), tezacaftor (T) and ivacaftor (I) in people with cystic fibrosis (pwCF)...ISC was measured after sequential addition of 100 M amiloride, 10 M forskolin (Fsk) and 100 M 3-isobutyl-1-methylxanthine (IBMX), 10 M I, 10 M CFTRinhibitor-172 (CFTRinh172) and 100 M ATP... Our results show significantly greater restoration of CFTR function in F508del/F508del HNEC treated with VTI compared to ETI. These results are in line with the improved sweat chloride values seen in the clinical trial.Supported by Ministry of Health of the Czech Republic, grant no NU23-07-00079."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Health outcomes for PwCF switching from a CFTR modulator therapy (CFTRm) to elexaftor/tezacaftor/ivacaftor (ETI) compared with those starting on ETI naively. A study using Irish registry data (ECFS 2025) - "This preliminary analysis suggests that despite C2's higher baseline BMI, PwCF who switched from Ivacaftor displayed similar patterns to modulator-nave patients and those who switched from a less effective CFTRm. Further analysis will include 2024 data, and stratification by genotype and disease severity."

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

How not to overlook a person with cystic fibrosis eligible for CFTR modulator therapy in a cystic fibrosis registry (ECFS 2025) - "The tiles display the number of assigned pwCF (their list is generated on click), all CFTRm treatment options with the first-line treatment listed first and information on region-specific regulatory approval (i.e. FDA approved only, EMA approved, EMA pending). Using this new interactive tool, 608 (84%) Czech pwCF were identified as eligible for one or more CFTRm drugs according to the EMA (584 for ETI as first line, 8 for LUM/IVA, 16 for IVA); 17 more will become eligible as they reach the minimum age. A further 36 pwCF are qualified for ETI or TEZ/IVA according to the FDA. This module allows the categorisation of pwCF based on age and genotype related indication criteria for CFTRm therapy, takes into account differences between FDA and EMA approved indications and can be easily adapted in case of any changes in eligibility. The system can serve as a model for other registries as it greatly simplifies the identification of all eligible pwCF for CFTRm."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Two-year longitudinal analysis of CFTR modulator therapy on liver fibrosis indices in children with cystic fibrosis (ECFS 2025) - "In this single-center observational study we prospectively evaluated these in pwCF aged 6-17 years on lumacaftor/ivacaftor (Lum/Iva) or Elezacaftor/Tezacaftor/Ivacaftor (ETI) therapy, followed at the CF center of Florence, Italy. AST-to-Platelet Ratio Index (APRI), GGT-to-Platelet Ratio (GPR), Fibrosis-4 (FIB-4), platelets, AST, ALT, GGT values were collected before and 12 months after Lum/Iva in F508del homozygous pwCF and 12 and 24 months after ETI in pwCF with at least one F508del variantFor APRI and GPR, the thresholds for Advanced CF Liver Disease (aCFLD) were according to Sellers et al. ETI decrease blood platelets in children and adolescents with CF, affecting the results of liver indices. These results warrant further validation and investigation for clinical significance."

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

Proteomic analysis of nasal lavage fluid and sputum samples in people with cystic fibrosis during 24 months of treatment with elexecaftor/tezacaftor/ivacaftor - The RECOVER study (ECFS 2025) - "ETI treatment is associated with differential expression of proteins involved in immune responses, particularly the complement cascade and proteins implicated in the protease-antiprotease imbalance. Sputum samples displayed very clear distinctions in proteome profiles before and after treatment, unlike NLF samples. NLF and sputum proteomes displayed limited similarity."

Omic analysis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Respiratory Diseases