Orkambi (lumacaftor/ivacaftor) / Vertex - LARVOL DELTA

Maternal and fetal outcomes associated with CFTR modulator use during pregnancy: a scoping review. (PubMed, Eur Respir Rev) - "We analysed clinical studies, registry data and related literature published between 2003 and 2025 to assess reported differences in lung function, birth weight, pregnancy and neonatal complications, mode of delivery and screening biomarkers among pregnancies in women with CF treated with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor, compared with pregnancies not exposed to CFTRm.Available evidence suggests that elexacaftor/tezacaftor/ivacaftor may improve maternal health through better lung function and nutritional status, while inadvertent fetal drug exposure has not been clearly associated with serious adverse outcomes. There is also insufficient evidence to establish the safety of infant exposure or prolonged maternal CFTRm use during lactation. This review highlights the need for future studies evaluating dose optimisation, long-term follow-up of infants and children, and integration of registry data to better define the..."

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

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

A functional comparison of readthrough agent ELX-02 across a wide range of nonsense CFTR variants. (PubMed, J Cyst Fibros) - "ELX-02 induces limited and highly heterogeneous CFTR rescue across nonsense variants. PDIO-based functional screening provides a framework to guide patient selection and stratification for future readthrough therapy trials."

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

Effect of CFTR modulators on glucose tolerance in children with cystic fibrosis: anage- and sex-matched cohort study (NACFC 2026) - " 80 treated children (29 males) were matched, 27 on LUM/IVA and 53 on ETI... We did not observe any statistically significant effects of CFTR modulator therapy on glucose metabolism. Modulator-specific in-depth analyses are warranted. Table 1 Baseline demographic and metabolic characteristics of participants in the control and CFTRm treated groups."

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

ENHANCE: Establishing Natural History in an Advanced New CF Care Era (NACFC 2026) - "At the time of submission, baseline data is available to date on 190 participants (mean age 3.3, [SD 2.2]), and one year follow up data on 104 participants (3.7[2.0]). Recruitment is ongoing. At baseline 90 children were on no modulator, 20 were on Ivacaftor (IVA), 47 were on Elexacaftor/tezacaftor/ivacaftor (ETI), 32 were on Lumacaftor/Ivacaftor (LI)."

Metastases

LCI5 as a Trial Endpoint in Cystic Fibrosis (NACFC 2026) - "In PROSPECT, LCI5 detected the lumacaftor/ivacaftor treatment effect at 1 month (-0.34; 95% CI -0.52, -0.17; p < 0.001), 3 months (-0.20; -0.42, 0.02; p = 0.07), 6 months (-0.31; -0.48, -0.13; p = 0.001) and 12 months (-0.29; - 0.57, -0.00; p = 0.047), consistent with the published LCI2.5 findings [3]... The shorter LCI5 test captures clinically relevant changes across multiple clinical settings in both children and adults with CF. While treatment effects were smaller, variability in change scores was consistently lower for LCI5 than LCI2.5."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Effect of CFTR Modulator Therapy on the Risk of CF-Related Diabetes (NACFC 2026) - "While highly effective modulator therapy (HEMT), including ivacaftor and elexacaftor/tezacaftor/ivacaftor (ETI), improves cystic fibrosis transmembrane conductance regulator (CFTR) function, its impact on CFRD pathogenesis remains uncertain, with conflicting published data [1]. These cross-sectional analyses indicate that among those with similarly severe CFTR dysfunction at baseline, HEMT (ivacaftor and ETI) is associated with 25-34% reduction in CFRD prevalence, while non-HEMT (lumacaftor/ivacaftor) is not. Longitudinal analyses are needed to establish time- and age-dependence to help determine whether HEMT prevents or delays CFRD development."

Cystic Fibrosis • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Respiratory Diseases • CFTR

Systemic Effects of CFTR Modulators on the Plasma and Serum Proteome (NACFC 2026) - "The CFTR modulator drug combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, ETI) has markedly improved clinical symptoms, but its broader molecular and systemic effects remain to be fully elucidated. We employed mass spectrometry-based proteomics to compare the plasma and serum proteomes of people with CF treated with the earlier, less effective lumacaftor/ivacaftor (LUM/IVA) combination against those receiving the more potent ELX/TEZ/IVA therapy... This study provides a comprehensive resource that enhances our understanding of CFTR modulator-driven proteome alterations, offering insights into both systemic and local protein regulation in CF. Our findings indicate that ELX/TEZ/IVA promotes broader systemic health improvements, providing critical insights that could shape future therapeutic strategies in CF."

Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Respiratory Diseases • CFTR • SFTPB

Association Between CFTR-Modulated Sweat Chloride Concentrations and Clinical Outcomes Across the CF Population: Top-Line Results From the CHEC-SC Study (NACFC 2026) - " The CHEC-SC study cohort included 4248 participants with mean age 19.6 years (range 0.8 - 77.2) from the years 2018 to 2024 and obtained 564, 779, 692, and 2213 SC values on ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor, respectively. Interim results suggest that CFTR modulated SC was nonlinearly associated with annualized PEx rate, indicative of post-modulator SC thresholds that may be associated with differential post-modulator PEx rates across the CF population."

Clinical • Clinical data

Deferring CFTR Modulator Use: Outcomes and Reasons in Pediatric People With Cystic Fibrosis (NACFC 2026) - "In the deferral group 2 (15.4%) deferred ivacaftor/lumacaftor, 3 (23%) ivacaftor, and 8(61.5%) elexacaftor/tezacaftor/ivacaftor. In this pediatric cohort the perceived lack of benefit and concerns about adverse effects were the most common reasons for deferral of CFTRm. Even in this younger age group starting CFTRm improved height and ppFEV1. Sharing real-world data including potential for lung function decline and working to coproduce a plan may help bridge some CFTRm hesitancy."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Pediatrics • Respiratory Diseases • Solid Organ Transplantation • CFTR

Early CFTR modulation and clinical outcomes in preschool cystic fibrosis. (PubMed, Pediatr Res) - "This commentary discusses Presti et al.'s multicenter prospective study evaluating lumacaftor/ivacaftor therapy in preschool children with cystic fibrosis homozygous for F508del. The findings provide important real-world evidence that early CFTR modulation improves biomarkers of CFTR function, pulmonary outcomes, and early lung physiology while maintaining an acceptable safety profile. These data support the broader concept that intervention during early childhood may offer an opportunity to modify disease progression before irreversible organ damage develops."

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

ADHERENCE PATTERNS AND THEIR DETERMINANTS TO CFTR MODULATORS IN FRANCE. (PubMed, Respir Med) - "We included pwCF (>6 years) who initiated at least one CFTRm (ivacaftor or lumacaftor/ivacaftor) between 2012 and 2020 and were treated for at least six months...Socioeconomic disadvantage was also associated with nonoptimal adherence. This study highlights the need for age-tailored interventions to support long-term adherence, revealing a decline among adolescents and young adults, along with a specific pattern among children, which may relate to prescribing practices at treatment initiation."

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

Pancreatitis Reporting With CFTR Modulators: A FAERS Pharmacovigilance Disproportionality Analysis (ACG 2026) - "After two-step deduplication, reports were screened for pancreatitis using a broad 36-term MedDRA dictionary and for exposure to four CFTR modulator regimens: elexacaftor/tezacaftor/ivacaftor (ETI), ivacaftor, lumacaftor/ivacaftor, and tezacaftor/ivacaftor. Among 8,648,164 deduplicated FAERS reports, 20,008 (0.23%) involved CFTR modulators and 32,242 (0.37%) included a pancreatitis-related term. Of CFTR modulator reports, 248 (1.24%) included pancreatitis, vs a background rate of 0.37% (p< 0.001). ETI accounted for 160 cases (64.5%), followed by ivacaftor 57 (23.0%), lumacaftor/ivacaftor 23 (9.3%), and tezacaftor/ivacaftor 20 (8.1%)."

Adverse events • Cystic Fibrosis • Genetic Disorders • Immunology • Pancreatitis • Respiratory Diseases • CFTR

Orkambi in Patients with Cystic Fibrosis and Severe Liver Disease (ANZCTR) - P1 | N=30 | Completed | Sponsor: Dr Adeline Lim | Recruiting ➔ Completed

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

An Integrated Quality by Design RP-UPLC Method for Lumacaftor and Ivacaftor in Human Plasma. (PubMed, Biomed Chromatogr) - "The retention times were 1.45, 1.77, and 1.99 min for EMT, IVA, and LUMA, respectively. The method is reliable, rapid and selective, exhibiting excellent linearity, precision, and accuracy, complying with USFDA guidelines."

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

Cystic Fibrosis Mortality Trends 1999-2024-A CDC Wonder Study. (PubMed, Adv Respir Med) - "The sequential approval of CFTR modulators ivacaftor (2012), lumacaftor/ivacaftor (2015), tezacaftor/ivacaftor (2018), and elexacaftor/tezacaftor/ivacaftor (2019) has transformed CF care, but population-level mortality trends across therapeutic periods have not been comprehensively assessed. The shift in the sex-based death count ratio and the concentration of remaining deaths in the South are hypothesis-generating observations that require confirmation with individual-level data. These ecological findings cannot establish causation, as concurrent changes in supportive care, lung transplantation practices, and COVID-19 pandemic effects may have contributed to the observed trends."

Journal • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Transplantation • CFTR

Real-life application of the Optical Beta-Adrenergic Sweat Test for people with cystic fibrosis. (PubMed, Pulm Pharmacol Ther) - "Among the PwCF, 39 were treated with various combinations of the CFTR modulators, including Lumacaftor/Ivacaftor (LI), Tezacaftor/Ivacaftor (TI) and/or Elexacaftor/Tezacaftor/Ivacaftor (ETI). In six PwCF, who underwent at least two different CFTR-targeted therapies, we also assessed lung function and nasal potential difference (NPD) in addition to ST, SDN, and the C/M ratio. We propose OBAST as a reliable complementary tool to standard tests, especially valuable when CFTR-targeted drugs are not approved for rare CFTR genotypes, when clinical response appears limited, and/or when sweat [Cl-] results are inconclusive."

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

LONGITUDINAL IMPACT OF LUMACAFTOR/IVACAFTOR THERAPY ON HEPATOBILIARY BIOCHEMISTRY AND IMAGING BIOMARKERS IN CHILDREN WITH CYSTIC FIBROSIS: PROSPECTIVELY COLLECTED SINGLE-CENTER OBSERVATIONAL DATA (ESPGHAN 2026) - "Conclusions Although no significant improvement in liver fibrosis was detected by LSM over 36 months of LUM/IVA therapy, improvements in biochemical indices and transaminase levels suggest a potential beneficial effect on CFHBI in cwCF. (NKFIH 138929, CF Trust NU-00600) Contact e-mail address [email protected]"

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

Pancreatitis reporting with CFTR modulators: a faers pharmacovigilance disproportionality analysis (IDDF 2026) - "After two-step deduplication, reports were screened for pancreatitis using a broad 36-term MedDRA dictionary and for exposure to four marketed CFTR modulator regimens: elexacaftor/tezacaftor/ivacaftor (ETI), ivacaftor, lumacaftor/ivacaftor, and tezacaftor/ivacaftor. Conclusions In FAERS, pancreatitis was reported disproportionately more often with CFTR modulators than with other drugs, and the signal persisted across all four regimens and in sensitivity analyses. These findings support a safety signal that warrants clinical awareness and further study.Download figure Open in new tab Download powerpoint Abstract IDDF2026-ABS-0334 Figure 1 Download figure Open in new tab Download powerpoint Abstract IDDF2026-ABS-0334 Figure 2"

Adverse events • Cystic Fibrosis • Genetic Disorders • Immunology • Pancreatitis • Respiratory Diseases • CFTR

Real-Life Experience With a Generic Formulation of Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis With Responding Variants. (PubMed, Pediatr Pulmonol) - "ETIgf demonstrates robust clinical efficacy and safety, mirroring results reported for the originator. These findings highlight the viability of affordable generic modulators in expanding global access to life-changing therapy."

Journal • Observational data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • 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

Comparison of Long Term Effects of Treatment of Different CFTR Modulators in People With Cystic Fibrosis. (PubMed, Pediatr Pulmonol) - "CFTRm - particularly ELX/TEZ/IVA - demonstrated substantial clinical benefits across age groups. The treatment effect varied over time in the majority of patients. Different CFTRm's impact on respiratory function, nutritional status, and well-being underscores the importance of personalized approaches in CF care."

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

Real-life effectiveness and safety of lumacaftor/ivacaftor in preschool children with cystic fibrosis: data from an italian multicentre study. (PubMed, Pediatr Res) - "LUM-IVA therapy in preschool children with CF shows significant real-world improvements in sweat chloride, exacerbations, weight, and LCI over 12 months, with an acceptable safety profile. It provides crucial real-world, observational data on LUM-IVA effectiveness and safety. The findings support the early use of LUM-IVA in young children with CF and potentially mitigate early progressive CF damage."

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

Effect of discontinuation and reduction of respiratory cotherapies on the effectiveness of CFTR modulators. (PubMed, J Cyst Fibros) - "This real-world study revealed a high rate of respiratory cotherapy discontinuation or reduction during the year following LUM/IVA or IVA initiation, without measurable clinical impact."

Journal

Acne in Cystic Fibrosis: Tips for Prescribing Isotretinoin in the Genomodulatory Era. (PubMed, Case Rep Dermatol Med) - "The package insert says that vitamin A supplementation should be stopped, presenting a therapeutic dilemma. We review the literature and previous reports of isotretinoin use in patients with CF to provide guidance on how to successfully treat acne while minimizing adverse effects, including in patients on genomodulatory therapy."

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