PRS31 Modelling Survival of People with Cystic Fibrosis (PWCF) Aged ≥12 YEARS Homozygous for the F508DEL Mutation Treated with Ivacaftor/Tezacaftor/Elexacaftor and Ivacaftor (IVA/TEZ/ELX)

Abstract

IVA/TEZ/ELX is a novel cystic fibrosis transmembrane conductance modulator (CFTRm) therapy approved by the European Medicines Agency to treat the underlying cause of disease for pwCF aged ≥12 years homozygous for the F508del mutation (F/F) or heterozygous for F508del and a minimal function mutation. A simulation model was used to estimate survival benefit of IVA/TEZ/ELX in F/F pwCF. A validated, lifetime, patient-level simulation model was used to estimate median survival in a simulated cohort of F/F pwCF aged ≥12 years in the United Kingdom (UK) treated with: IVA/TEZ/ELX+best supportive care (BSC), tezacaftor/ivacaftor (TEZ/IVA)+BSC, and BSC-alone. Age-specific mortality hazards from the 2008 UK CF Registry were combined with a Cox proportional hazards model to predict survival based on several risk factors in pwCF. Clinical efficacy inputs for IVA/TEZ/ELX+BSC and TEZ/IVA+BSC were derived from an indirect treatment comparison conducted using data from the IVA/TEZ/ELX Phase 3b study (NCT04105972) and TEZ/IVA Phase 3 study (NCT02347657). CFTRm impact on long-term lung function decline was based on TEZ/IVA data. Median projected survival in BSC-treated pwCF was 37.8 years; median projected survival increased to 47.9 years in TEZ/IVA-treated pwCF and 59.1 years in IVA/TEZ/ELX+BSC-treated pwCF, leading to an incremental survival increase with IVA/TEZ/ELX+BSC of 11.2 years versus TEZ/IVA+BSC and 21.3 years versus BSC-alone. Patients initiating IVA/TEZ/ELX+BSC treatment at age 12 years were projected to live 15.6 years more than TEZ/IVA+BSC-treated (74.4 vs 58.8 years) and 37.5 years more than BSC-alone–treated (74.4 vs 36.9 years) pwCF. At 10 years, 83% of IVA/TEZ/ELX+BSC-treated pwCF were alive versus 73% and 57% of TEZ/IVA+BSC-treated and BSC-alone–treated pwCF, respectively. Based on these simulations, treatment with IVA/TEZ/ELX+BSC is projected to substantially increase survival for pwCF aged ≥12 years with the F/F genotype in the UK. Treatment initiation at the youngest indicated age is projected to provide even greater survival benefit.