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

Adverse Events Associated with CFTR Modulator Therapy: Experience from a Tertiary Care Center. (PubMed, Turk Arch Pediatr) - "Cystic fibrosis transmembrane conductance regulator modulators are generally well tolerated in the pediatric population. Most adverse events are mild, transient, and manageable through routine monitoring and temporary cessation, allowing for the safe continuation of therapy."

Adverse events • Journal • Cystic Fibrosis • Dermatology • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases • CFTR

Prenatal CFTR modulator therapy for fetal cystic fibrosis: Emerging evidence, clinical considerations, and future directions. (PubMed, Pregnancy (Hoboken)) - "The advent of CFTR modulator therapies (CFTR modulator)-most notably elexacaftor/tezacaftor/ivacaftor (ETI), approved for children and adults with CF who carry responsive variants, and the recently approved vanzacaftor/tezacaftor/deutivacaftor (VTD), currently indicated for older pediatric and adult populations-has transformed long-term health outcomes and substantially increased the number of pregnancies among individuals with CF. While continuation for maternal CF is supported by available evidence (although not label-approved), fetal-indication use remains investigational. Robust counseling, interdisciplinary coordination, and structured monitoring are essential, alongside ongoing research to define therapeutic windows, safety, and long-term outcomes."

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

Urticarial Drug Eruption Following Elexacaftor/Tezacaftor/Ivacaftor Therapy in a Child With Cystic Fibrosis (EADV 2026) - "The eruption regressed with oral cetirizine therapy despite continuation of ETI treatment, and no recurrence or progression was observed during follow-up. Recognition of these eruptions is important for accurate diagnosis and differentiation from viral exanthems and erythema multiforme. Clinicopathological correlation remains essential in establishing the diagnosis of ETI-associated cutaneous drug reactions."

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

Lichenoid Drug Eruption Associated with Elexacaftor/Tezacaftor/Ivacaftor Therapy (EADV 2026) - "As ETI therapy was maintained, treatment with twice-weekly phototherapy combined with topical clobetasol was initiated, leading to marked clinical improvement...Phototherapy was discontinued after seven months, and hydroxychloroquine after four months, with sustained remission and no evidence of recurrence to date...This observation broadens the spectrum of dermatological effects potentially linked to ETI and emphasizes the need for heightened clinical awareness of atypical presentations in patients undergoing this treatment. The recognition and reporting of rare adverse events such as this are crucial for strengthening pharmacovigilance, informing clinical practice, and optimizing the long-term care and safety of patients with cystic fibrosis."

Acne Vulgaris • Atopic Dermatitis • Cystic Fibrosis • Dermatitis • Dermatopathology • Genetic Disorders • Immunology • Inflammation • Lichen Planus • Pruritus • Respiratory Diseases • IFNG

Concentrated Socioeconomic Disadvantage Predicts Center-Level Lung Function in Cystic Fibrosis: Stronger Gradients in Pediatric Than Adult Programs in the Post-Elexacaftor/Tezacaftor/Ivacaftor Era (NACFC 2026) - "In the post-ETI era, whether a CF center is in a wealthy or educated community does not predict outcomes. What does predict worse FEV1 is concentrated disadvantage. This gradient is stronger in pediatric programs, consistent with children's shorter time on ETI."

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

Evaluation of Depression and Anxiety Symptoms After Starting Vanzacaftor/Tezacaftor/Deutivacaftor (NACFC 2026) - "Postmarketing data for elexacaftor/tezacaftor/ivacaftor (ETI) describe serious neuropsychiatric events, such as anxiety, depression, suicidal thoughts or behaviors, and sleep disturbances [2]. Most patients initiating VTD did not report adverse mental health effects, and among those who perceived a change in mental health symptoms, the majority reported an improvement. However, a subset experienced worsening mental health symptom, underscoring the importance of routine mental health screening, multidisciplinary monitoring, and ongoing assessment during VTD initiation and treatment. Larger, multicenter longitudinal studies are needed to better characterize the long-term mental health effects of VTD."

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

Prenatal CFTR Modulator Exposure: From Pregnancy to Infancy and Beyond (NACFC 2026) - "Background: Multiple case reports and accumulating series describe potential benefit from in utero rescue of CFTR-related disease utilizing elexacaftor/tezacaftor/ivacaftor (ETI)... Prenatal ETI exposure shows promise in improving outcomes for CF infants, both in resolving meconium ileus and restoring early pancreas function. Additional data on infant outcomes beyond the first few weeks of life remains of high interest."

Cataract • Ophthalmology

Bile Acids as Potential Immunomodulatory Signals (NACFC 2026) - " Plasma samples from pwCF pre- and post-elexacaftor/tezacaftor/ ivacaftor (ETI) were assessed for BAs and related metabolites...Additional human samples (plasma and airway) pre- and post-vanzacaftor/tezacaftor/deutivacaftor are under analysis for untargeted metabolomics, targeted BA and oxylipin quantification, RNA expression, and cytokines...However, BA-treated M2-polarized (dexamethasone) macrophages had a blunted transcriptional response to LPS stimulation... scRNA-seq data and in vitro experiments confirmed that lung macrophages express BA receptors at physiologically relevant levels, while metabolomics studies revealed persistent BA alterations in CF. Ongoing studies using alternative differentiation conditions, repeated BA exposure, and human samples will clarify whether BAs contribute to macrophage-mediated bacterial tolerance in CF."

Immunomodulating

Annals of ATS-- Impact of 2 years of Treatment with Elexacaftor/Tezacaftor/Ivacaftor on Longitudinal Changes in Structural Lung Disease in People with Cystic Fibrosis: Results from the RECOVER Trial (NACFC 2026) - No abstract available

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

Development of Metabolic Syndrome in People with Cystic Fibrosis After Prolonged Exposure to Elexacaftor/Tezacaftor/Ivacaftor (NACFC 2026) - "Short- and long-term ETI use was associated with adverse cardiometabolic changes, including increased MetSyn and worsening lipid and blood pressure profiles. Although MetSyn cases appeared lower at 5 years, this was no longer evident after accounting for GLP-1 RA or statin use, suggesting the improvement may reflect the effect of medical intervention. Similarly, the decline in stage 2 HTN at 5 years potentially reflects increased recognition and treatment of HTN."

Cardiovascular • Cystic Fibrosis • Dyslipidemia • Genetic Disorders • Hypertension • Immunology • Metabolic Disorders • Obesity • Respiratory Diseases

Inhibition of Translation Initiation as a Unifying Mechanism for Rescue of CFTR Nonsense Variants (NACFC 2026) - "Studies included treatment comparisons to established read-through agents (G418), nonsense mediated decay (NMD) inhibitors (SMG1i), mRNA amplifiers (PTI-428), and CFTR modulators (elexacaftor-tezacaftor-ivacaftor, ETI; vanzacaftor-tezacaftor-ivacaftor, VTD). Earlier work has established that RPL12 knockdown diminishes rates of translation initiation and elongation through effects on GC-rich codons. RPL8 suppression reduces ribosome fidelity by causing structural changes to functional centers of the 40S and 60S subunits. We therefore propose that RPL12 knockdown elicits CFTR PTC read-through by abrogating release factor interactions and inducing peripheral stabilization of partially synthesized proteins through interference with initiation and elongation factors."

CFTR • EIF4A3 • EIF4E • EIF4G1 • RPL8

NMD Inhibition Unlocks Readthrough-Free Modulator Rescue of Nonsense Variants in CFTR at TM12-NBD2: A G551D-Like Precision Path (NACFC 2026) - "While readthrough drugs were advanced to clinical trials (e.g., Ataluren, ELX- 02) to enable translation past PTCs and suppress NMD, these trials have failed to show meaningful benefit...In primary airway cultures (W1282X/W1282X, n = 4; S1255X, n = 1), activity improved from ∼0.1 to 3.4–3.9 μA/cm2 with KVS0001 + next-generation modulators (VTI/Alyftrek) ( ∼27% of WT), with similar rescue using ETI (Trikafta) or ivacaftor-based regimens... Taken together, for TM12–NBD2-proximal nonsense variants, NMD inhibition alone without readthrough agents unlocks clinically available modulator rescue, offering a path to expand therapy to pwCF currently who currently have no options. Because NMD is a core transcriptome surveillance pathway, large-animal PK/tox studies in a CFTR PTC reporter SRM2 pig model are warranted. Establishing this NMD-first model for PTC variants could provide a framework for treating all PTC variants."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Therapeutic Potential of a Novel eRF3 Degrader to Induce Translational Readthrough of CFTR Nonsense Mutations (NACFC 2026) - "However, the addition of CFTR modulators (Elexacaftor/tezacaftor/ivacaftor) provided no further benefit which is concordant with known amino acids inserted upon readthrough of the R1162X allele... SRI-50561 is a novel eRF3 degrader that induces translational readthrough and restores substantial CFTR function across various PTC alleles in primary human cell models. These findings support the ongoing development of SRI-50561 as a potential monotherapy for CF patients with nonsense mutations"

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR • GSPT1

XeMRI to Predict Pulmonary Exacerbations in People with Cystic Fibrosis on Elexacaftor-Tezacaftor-Ivacaftor (NACFC 2026) - "In this cohort of adults and children with CF on ETI, LCI, and VDP performed better than ppFEV1 in discriminating those at higher risk for future PEx. ppFEV1 demonstrated the lowest predictive performance across analyses, underscoring the declining diagnostic utility of spirometry in pwCF on ETI. These findings suggest that XeMRI and MBW may provide additional value for identifying individuals at an increased risk of future PEx in the current landscape of widespread CFTR modulator therapy."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Exhaled Volatile Organic Compound Biomarkers for Pulmonary Exacerbations in Children With CF (NACFC 2026) - " 22 children with CF (median age 13 years, 61% homozygous F508del, median FEV1pp 90, 95% receiving elexacaftor-tezacaftor-ivacaftor) provided 55 breath samples... Longitudinal analysis of exhaled breath VOCs offers a robust approach for identifying repeatable and biologically relevant markers associated with PEx in CF. Further investigation is warranted to elucidate the role of inflammation-driven changes in terpene pharmacokinetics. Correlation of VOC expression with ΔFEV1pp further implicated saturated hydrocarbons as the dominant functional group, consistent with findings from our previous pilot study."

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

Elevated Myeloperoxidase Activity in Non-CF Bronchiectasis and Shared Metabolite Profiles in CF and Non-CF Bronchiectasis (NACFC 2026) - "CF patients included individuals offor on CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor, or ETI)... Building on our previous work in CF, the data suggests the relevance of several biomarkers in NCFBE and CF, providing opportunities to further explore disease pathophysiology and progression. Intriguingly, some metabolites (guanine, maltose) were inversely correlated with MPO and may reflect pathological targets of MPO effector functions. Despite the heterogeneity of NCFBE etiologies, the pathological burden associated with the active release of MPO and other powerful effectors by GRIM neutrophils in patient-derived samples and its correlation with clinical outcomes represents a potential unifying mechanism of pathogenesis."

Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • MPO

Impact of Treatment with Elexacaftor/Tezacaftor/Ivacaftor on Exhaled Nitric Oxide in Cystic Fibrosis: The RECOVER Study (NACFC 2026) - "These data suggest that FeNO in pwCF has a stronger relationship to structural lung disease, particularly mucus plugging, than with lung function by spirometry. The isolated increase in FeNO with ETI in the 12 + F508del homozygous cohort is incompletely explained by changes in structural lung disease or lung function."

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

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

Evaluation of Elexacaftor/Tezacaftor/Ivacaftor Effect on Fecal Elastase After at Least Six Months of Therapy in Pediatric Cystic Fibrosis Patients (NACFC 2026) - "We evaluated the effect of ETI therapy on exocrine pancreatic function as measured by FE in pediatric CF patients. Our results indicate that ETI may result in improvement in pancreatic function, as evidenced by an increase in FE to > 200 mcg/g. ETI therapy has allowed some pediatric CF patients to discontinue PERT therapy."

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

Implementation of a Pharmacist-Led CFTR Modulator Initiation and Management Program Utilizing Expanded Scope of Practice Authority (NACFC 2026) - " This retrospective cohort study evaluated individuals with CF initiated on elexacaftor/tezacaftor/ivacaftor (Trikafta) or vanzacaftor/tezacaftor/deutivacaftor (Alyftrek) at an accredited CF center between January 2025 and February 2026. A pharmacist-led CFTR modulator initiation and management program utilizing expanded scope of practice authority enabled independent initiation, monitoring, and dose adjustment of CFTR modulators. This model optimized therapy management while reducing provider burden and improving care efficiency. Expanded pharmacist scope of practice represents a scalable strategy to enhance CFTR modulator management and multidisciplinary CF care delivery."

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

Standardizing Safety Monitoring of Highly Effective Modulator Therapy (HEMT) Across Adult and Pediatric Cystic Fibrosis (CF) Clinics (NACFC 2026) - "Updated FDA guidance in early 2025 recommended more frequent liver function test (LFT) monitoring when initiating elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (VTD) therapy, further emphasizing the importance of identifying adverse effects (AE). The project aim of ≥ 80% AE assessment was achieved in both clinics. AE documentation improved in the adult clinic as workflows became standardized, while rates declined in the pediatric clinic during a transition to a more intermittent, as-needed pharmacy model. Future efforts focus on maintaining consistent AE assessment when a pharmacist is not present and refining AE management approaches, including dose modification of HEMT in response to AEs."

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

Pharmacogenomics Guides Elexacaftor-Tezacaftor-Ivacaftor-Associated Adverse Effect Management and Prevention (NACFC 2026) - "Pharmacist and pulmonologist utilized PGx results to guide patient's individualized target dose and/or dosing titration plan if rechallenged on ETI or transitioned to vanzacaftortezacaftor-deutivacaftor. Incorporating a genotype guided approach for pediatric pwCF utilizing PGx to evaluate ETI adverse effects and guide individualized CFTR modulator dosing may reduce time offtherapy and prevent CFTR associated adverse effects."

Adverse events • Biomarker • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR • CYP3A4 • CYP3A5 • UGT1A1

Outcomes of Vanzacaftor/Tezacaftor/Deutivacaftor in People With Cystic Fibrosis Who Switch From Highly Effective Modulator Therapy (NACFC 2026) - "Vanzacaftor/tezacaftor/deutivacaftor (VTD) is a once daily CFTR modulator shown to be noninferior to elexacaftor/tezacaftor/ivacaftor (ETI) in clinical trials. This study found that switching from HEMT to VTD does not appear to affect ppFEV1 or liver enzymes in PwCF. It significantly improved adherence in pediatric PwCF and reduced the number of PEx in adult PwCF. Our study suggests that VTD is a comparable treatment option to ETI and may be beneficial for patients who struggle with adherence; additional monitoring for adverse effects is needed to optimize treatment."

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

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

Factors Predicting Return of Pancreatic Exocrine Function in People with Cystic Fibrosis (NACFC 2026) - "We included all pwCF who were taking HEMT (elexacaftor/tezacaftor/ivacaftor and vanzacaftor/tezacaftor/deutivacaftor.) Patients who were ineligible for HEMT were excluded, as were patients who have been PS since birth. Our data reinforces what has previously been identified, that age of initiation is an important factor in determining who achieves PS [3]. Likely due to the ability of HEMT to halt progression of irreversible pancreatic damage. This is also likely reflected in our finding that years on HEMT are also inversely correlated with achieving PS."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases