olacaftor (VX-440) / Vertex - LARVOL DELTA

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). (PubMed, Cochrane Database Syst Rev) - "There is insufficient evidence of clinically important effects from corrector monotherapy in pwCF with F508del/F508del. Additional data in this review reduced the evidence for efficacy of dual therapy; these agents can no longer be considered as standard therapy. Their use may be appropriate in exceptional circumstances (e.g. if triple therapy is not tolerated or due to age). Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar small improvements in QoL and respiratory function with lower pulmonary exacerbation rates. While the effect sizes for QoL and FEV still favour treatment, they have reduced compared to our previous findings. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population,..."

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

Systematic review of corrector modulator therapy for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del) (NACFC 2023) - " Thirty-four RCTs were included (4,781 participants): eight monotherapy RCTs (4PBA, CPX, lumacaftor, cavosonstat, FDL 169), 15 dual-therapy RCTs (lumacaftor-ivacaftor or tezacaftor-ivacaftor), and 11 triple-therapy RCTs (elexacaftor-tezacaftor-ivacaftor [ETI], VX-659-teza-caftor-ivacaftor, VX-440-tezacaftor-ivacaftor, VX-152-tezacaftor-ivacaftor). There is no evidence to support monotherapy and limited evidence to support dual therapy for PwCF who have a class II CFTR gene variant. Clinically relevant differences were found in key outcomes in the triple therapy studies, and these demonstrated a better safety profile than lumacaftor-ivacaftor. There appears to be additional benefit of changing to triple therapy for PwCF already established on ivacaftor."

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

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del) (BTS WM 2022) - "Two authors then independently extracted data, assessed risk of bias and evidence quality (GRADE).Results A total of 34 RCTs were included (1754 participants); eight monotherapy RCTs (4PBA, CPX, lumacaftor, cavosonstat and FDL 169), fifteen dual-therapy RCTs (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and eleven triple-therapy RCTs (elexacaftor-tezacaftor-ivacaftor, VX-659- tezacaftor-ivacaftor, VX-440-tezacaftor-ivacaftor and VX-152-tezacaftor-ivacaftor). There were significant and clinically relevant differences found across outcomes in the triple therapy studies, with improved safety profile. More research is needed into assessing these therapies in paediatric patients and the longer-term safety profiles of these new therapies, but these early results suggest this will be a transformational intervention for pwCF with class 2 CFTR gene variants."

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