Real-world effects of lumacaftor/ivacaftor (LUM/IVA) in people with cystic fibrosis (pwCF): final results of a long-term safety study using US CF Foundation Patient Registry and UK CF Patient Registry data

Abstract

<b>Background:</b> LUM/IVA is indicated for the treatment of pwCF homozygous for <i>F508del</i><i>(F/F)</i>. <b>Aims and objectives:</b> This 5-year (y) safety surveillance study evaluated real-world evidence of safety in pwCF with <i>F/F</i> genotypes treated with LUM/IVA. <b>Methods:</b> The final analysis of this study included pwCF in US and UK CF registries aged ≥2 y treated with LUM/IVA in 2020. Outcomes were compared to an unmatched concurrent comparator cohort (COMP) of pwCF heterozygous for <i>F508del</i> and a minimal function mutation with no history of CFTR modulator use. Outcomes included death, organ transplantation, pulmonary exacerbations (PEx), hospitalizations, and complications. <b>Results:</b> US LUM/IVA cohort (n=1,739; mean [range] age=7.3 [2.0–59.9] y) had no deaths or organ transplants and had lower age-adjusted odds of PEx (OR=0.67; 95% CI: 0.54, 0.84), hospitalizations (OR=0.72; 95% CI: 0.60, 0.87), and complications (OR=0.90; 95% CI: 0.78, 1.04) than COMP (n=2,092; mean [range] age=14.8 [2.0–68.5] y). UK LUM/IVA cohort (n=853; mean [range] age=6.7 [2.0–47.0] y) had no deaths or organ transplants and had lower age-adjusted odds of PEx (OR=0.19; 95% CI: 0.13, 0.29), hospitalizations (OR=0.32; 95% CI: 0.24, 0.42), and complications (OR=0.86; 95% CI: 0.66, 1.11) than COMP (n=791; mean [range] age=16.8 [2.0–66.0] y). No new safety signals were identified. The results of the final-year safety analyses were consistent with the previous 4 annual analyses. <b>Conclusions:</b> The results of this study support the long-term safety of LUM/IVA use in pwCF aged ≥2 y. <b>Sponsor:</b> Vertex Pharmaceuticals Incorporated.