OBJECTIVES: To project survival impact of TEZ/IVA in F508del/RF patients ≥12 years

METHODS: Survival with TEZ/IVA plus best supportive care (BSC) vs BSC alone in the UK population was estimated using a lifetime simulation model. A UK CF reference mortality curve and Cox regression model were combined to predict survival based on risk factors, including percent predicted forced expiratory volume in 1 second (ppFEV), pulmonary exacerbations requiring hospitalisation/intravenous antibiotics (PEx_IV/IP), and weight-for-age z score (WFAz). Patient profiles were derived from baseline characteristics in the phase 3 trial EXPAND (NCT02392234). Published registry analyses were used to estimate disease progression inputs for BSC. A 6.8–percentage point increase in ppFEV and 0.05 increase in WFAz were applied to TEZ/IVA-treated patients over the first 8 weeks (trial duration) of the model, with subsequent reduction in annualized ppFEV decline of 47.1% based on long-term data from another CFTRm, ivacaftor. PEx_IV/IP rate was assumed to be 45.0% lower for TEZ/IVA vs BSC, based on numerical improvements observed in EXPAND. Sensitivity analyses varied TEZ/IVA impact on long-term ppFEV decline using 95% CI; a separate scenario assumed no direct treatment effect on PExIV/IP RESULTS: Mean baseline age and ppFEV of the simulated cohort were 35.6 years and 61.9%, respectively. The model estimates TEZ/IVA increases median survival by 8.3 years vs BSC (median age of death, 49.5 vs 41.2). In sensitivity analyses, assuming 31.5% and 70.1% reductions in rate of ppFEVdecline, median projected survival with TEZ/IVA was 7.2 and 9.7 years greater, respectively, vs BSC. Assuming no direct PEx_IV/IP impact, TEZ/IVA is projected to increase median survival by 6.3 years vs BSC.

CONCLUSIONS: TEZ/IVA is projected to improve survival for F508del/RF patients ≥12 years. Modeled results highlight the potential long-term value of TEZ/IVA for this population.