PRS2 Modelling Survival of People with Cystic Fibrosis (PWCF) Aged ≥12 YEARS Heterozygous for the F508DEL Mutation with a Minimal Function 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 or heterozygous for F508del and a minimal function mutation (F/MF). In the absence of long-term real-world data, a simulation model was used to estimate survival in the F/MF population receiving IVA/TEZ/ELX plus best supportive care (BSC) versus BSC-alone. A validated, lifetime, patient-level simulation model was used to estimate median survival of a simulated cohort of F/MF pwCF aged ≥12 years in the United Kingdom (UK) with and without IVA/TEZ/ELX treatment. 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 were derived from the Phase 3 study in the F/MF population (NCT03525444). IVA/TEZ/ELX impact on long-term lung function decline was based on other CFTRm data. Outcomes were also evaluated for a simulated cohort initiating treatment at age 12 years and using a 10-year model horizon. Median projected survival in pwCF on BSC was 37.8 years; median projected survival increased to 59.9 years in IVA/TEZ/ELX+BSC-treated pwCF, leading to an increase in incremental survival with IVA/TEZ/ELX+BSC of 22.0 years versus BSC-alone. pwCF initiating IVA/TEZ/ELX+BSC treatment at age 12 years were projected to live 36.9 years more than pwCF receiving BSC-alone (73.8 vs 36.9 years). At 10 years, 83% of pwCF receiving IVA/TEZ/ELX+BSC were projected to be alive versus 56% of patients receiving BSC-alone. Based on these simulations, treatment with IVA/TEZ/ELX+BSC is projected to increase median survival by more than 2 decades for F/MF pwCF aged ≥12 years in the UK. Treatment initiation at the youngest indicated age (i.e., age 12 years) leads to even greater projected survival benefits.