CFTR modulator / Sanofi - LARVOL DELTA

Stabilizers of CFTR NBD1 synergize with galicaftor (SION-2222) or SION-109 to enable full correction of ΔF508-CFTR (ECFS 2025) - "Sionna is advancing in clinical studies a portfolio of novel NBD1 stabilizers and complementary modulators with a goal to provide pwCF with innovative options. Based on preclinical data, Sionna modulator combinations, if successfully developed and approved, have the potential to provide dramatic improvements in clinical outcomes and quality of life for pwCF."

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

Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis. (PubMed, J Cyst Fibros) - "ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin)."

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

Use of CFTR modulators in special populations, part 1: Pregnancy and lactation. (PubMed, Pediatr Pulmonol) - "A scoping review of English articles from the period of January 1, 2012, to July 31, 2023, was conducted utilizing PubMed and EmBase databases with the following terms: "special population (pregnancy, lactation, breastfeeding)" AND "ivacaftor OR lumacaftor OR tezacaftor OR elexacaftor"; "cystic fibrosis transmembrane conductance regulator" AND "off label drug use." Search results were reviewed by title and abstract for duplications and relevance. Current safety data surrounding CFTR modulator use in the setting of pregnancy and lactation is relatively reassuring; however, long-term safety remains unclear, necessitating ongoing observation, and reporting by care teams. As such, treatment decisions should be individualized and coproduced."

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

Use of CFTR modulators in special populations, part 2: Severe lung disease. (PubMed, Pediatr Pulmonol) - "Safety and efficacy data surrounding cystic fibrosis transmembrane regulator (CFTR) modulator administration for people with CF (pwCF) and severe lung disease elect has remained unclear as a result of exclusion from key trials. A scoping review of English language articles from the period of 1 January 2012, to 31 July 2023 was conducted utilizing PubMed and EmBase databases with the following terms: "severe lung disease" OR "advanced lung disease" AND "ivacaftor OR lumacaftor OR tezacaftor OR elexacaftor"; "cystic fibrosis transmembrane conductance regulator" AND "off label drug use." Search results were reviewed by title and abstract for relevance. Twenty articles specific to CFTR modulator use in the setting of severe lung disease were included for review, with few specific to pediatric-aged pwCF. ELE/TEZ/IVA utilization in pwCF and severe lung disease appears to be devoid of the transient..."

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

Beyond SION-638: a novel series of highly potent stabilizers of NBD1 enable full correction of ΔF508-CFTR in a dual combination with Sionna CFTR modulators, providing a path to wild-type function. (NACFC 2023) - "Sionna is advancing a second series of highly potent first-in-class NBD1 stabilizers and complementary CFTR modulators to use in combination with NBD1. Development candidates from this series enable dual-modulator combinations that provide multiple potential paths to full restoration of CFTR function for most people with CF and are progressing toward clinical studies."

CFTR

Novel CFTR modulator combinations directly address the ΔF508-CFTR NBD1 stability defect and enable full CFTR correction (ECFS 2023) - "Sionna is advancing first-in class small molecules that robustly stabilize the CFTR NBD1 domain, and mechanistically complementary CFTR assembly correctors for use in combination. With NBD1-stabilizers as their base, Sionna combinations have the potential to provide CF patients with unprecedented improvement in ΔF508-CFTR maturation, trafficking, and function."

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

Use of CFTR modulators in special populations, part 3: Solid organ transplant. (PubMed, Pediatr Pulmonol) - "Modulator therapy has been reported to produce pulmonary and extra-pulmonary benefits in the CF population with SOT. Considerations for modulator therapy initiation ought to include modulator pharmacokinetics, concomitant medications, and transplant type due to the complex nature of SOT recipients."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hepatology • Immunology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • Solid Organ Transplantation • Transplantation