Symdeko (tezacaftor/ivacaftor) / Vertex - LARVOL DELTA

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

Evaluation of modulator therapy on mental health of patients with cystic fibrosis and their caregivers (ECFS 2025) - "Background: The cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug lumacaftor/tezacaftor/ivacaftor (ETI) was shown to improve the clinical symptoms of patients with cystic fibrosis (CF)... This result suggests that patients and caregivers who do not use modulators are at higher risk for anxiety and depression than those using modulators.Table 1: CFQ-RGroup 1Group 2PCFQ-R aged 6-11 Scale Score, n1: 12, n2: 12 median, Q1-Q3 median, Q1-Q3Physical 63,89 (44,44-75,0) 72,22 (63,84-83,32) 0.233Emotion 83,33 (77,09-87,50) 79,17 (66,66-83,33) 0.208Eat 55,56 (55,56-66,67) 66,67 (61,12-72,22) 0.207Treat 66,67 (66,67-66,67) 72,22 (66,67-83,34) 0.097Social 57,14 (52,38-64,29) 57,14 (54,76-69,05) 0.557Body 77,78 (66,67-100,0) 83,34 (66,67-100,0) 0.693Respiratory 87,50 (79,16-91,67) 83,33 (75,0-91,67) 0.551Digestive 100,0 (66,67-100,0) 66,67 (66,67-100,0) 0.633CFQ-R aged 12-13 Scale Score n1:3, n2:1Physical 79,22 (38,89-100,0) 38,89 (38,89-38,89) 0.346Emotion..."

Clinical • CNS Disorders • Cystic Fibrosis • Depression • General Anxiety Disorder • Genetic Disorders • Immunology • Mood Disorders • Psychiatry • Respiratory Diseases • CFTR

Dynamics of body composition in children with cystic fibrosis after receiving targeted therapy for 1 year (ECFS 2025) - "Inclusion criteria: children with cystic fibrosis who received Ivacaftor+lumacaftor and Elecsacaftor/ivacaftor/tezacaftor before and after 1 year of TT, aged 5 to 18 years, who signed an informed consent. An analysis of body composition in children with CF showed a significant increase in the proportion of fat mass after 1 year of TT, which should be considered as a risk of developing obesity and "latent obesity" (an imbalance towards an increase in fat mass to the detriment of the lean body mass) and the need for timely preventive measures. Further research is needed"

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

Safety assessment of the FAIR therapeutics CFTR modulators nesolicaftor, posenacaftor and dirocaftor in CF patients (ECFS 2025) - "Subjects either received background treatment with lumacaftor/ivacaftor or tezacaftor/ivacaftor or no CFTR modulator. The compounds were generally well-tolerated, with NES administered at up to 100 mg daily for 14 days, POS at up to 400 mg daily for 14 days, and DIR at up to 300 mg daily for 7 days. The DIR/POS/NES combination therapy was well tolerated with mostly mild-to-moderate, reversible AEs, and no SAEs attributed to the drugs."

Clinical • Cough • Diabetes • Gastrointestinal Disorder • Infectious Disease • Pain • Respiratory Diseases

The effect of gradual increase in control visit intervals on essential primary endpoints in children 2-18 year old with CF on ETI therapy (ECFS 2025) - "We expect comparable clinical outcomes between patients with bimonthly and monthly follow visits, suggesting that bimonthly monitoring is a safe approach for managing patients with CF on ETI therapy."

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

Sustainable effect of elaxacaftor/tezacaftor/ivacaftor on FEV1 and LCI over 2 years (ECFS 2025) - "ETI significantly and sustainably improved FEV1pp and LCI over a period of 2 yrs. Strongest improvement was observed for pwCF with moderate lung disease; but also young children and individuals with close to normal FEV1pp and LCI showed significant long-term improvements."

Pulmonary Disease • Respiratory Diseases

Assessment of the impact of the new born screening programme on growth and Pseudomonas aeruginosa infection in children with cystic fibrosis in Ireland: the Irish Comparative Outcomes Study (ICOS) (ECFS 2025) - "Findings reported significant benefits of early detection of CF in terms of improved growth parameters. However, Pa acquisition was determined predominantly by mutation status and modulator treatment."

Clinical • IO biomarker • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Respiratory Diseases • ICOS

Changes in health-related quality of life after the introduction of triple-modulator therapy in cystic fibrosis (ECFS 2025) - "Objective: The introduction of elaxacaftor/tezacaftor/ivacaftor (ETI) has led to improved symptoms and longer life expectancy in people with cystic fibrosis (pwCF)... Among adolescents/adults, ETI had a positive impact on HRQoL with improvements in most domains lasting two years after initiation. Fewer HRQoL domains improved in children and the effects seen were less prominent compared to adolescents/adults likely because children had better scores before ETI therapy in most HRQoL domains. In adolescents/adults, gains in HRQoL mirrored benefits in clinical endpoints as previously reported.Funding: Funded by Vertex Pharmaceuticals."

Clinical • HEOR • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Home Cough Monitoring Reveals Higher Nighttime Cough Burden in Children With Cystic Fibrosis Compared With Healthy Children (ATS 2025) - "This abstract is funded by: CFF 2024 Clinical Fellowship Research Award (MELZER24D0) Rational: Children with cystic fibrosis (cwCF) on elexacator/tezacaftor/ivacaftor (ETI) may have fewer clinical encounters as their health improves... Use of a passive bedside cough monitor detected nighttime cough in cwCF and HC. CwCF have more nighttime cough compared to HC, despite being relatively healthy and on ETI. Cough monitoring detected more frequent cough during periods of PEx."

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