OBJECTIVES: Estimate survival impact of TEZ/IVA in patients aged ≥12 years homozygous for the F508del mutation (F508del/F508del).

METHODS: Survival with TEZ/IVA vs. chronic symptomatic therapies (CST) was estimated using a lifetime simulation model. A 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) and pulmonary exacerbations requiring hospitalization/intravenous antibiotics (PEx). Patient profiles were derived from baseline data of F508del/F508del patients enrolled in phase 3 clinical trials. Disease progression inputs, including ppFEV decline, were derived from published registry analyses. TEZ/IVA patients gained 4.0 ppFEVpercentage points during the first 24 weeks of the model, based on trial results (NCT02347657), after which TEZ/IVA was assumed to reduce annualized ppFEV decline by 42.0%, based on long-term CFTRm data[1] decline and simulated an alternative cohort representing F508del/F508del aged ≥12 years in the US CF Foundation Patient Registry.

RESULTS: Mean baseline age and ppFEV of the simulated trial-based cohort were 25.7 years and 60.9 percentage points, respectively. Compared to CST, the model estimates TEZ/IVA increases median survival by 6.4 years (40.9 vs. 34.5). Alternatively, a 32.0% and 52.0% reduction in rate of ppFEVdecline vs. CST, increases median survival by 5.6 and 6.9 years, respectively. Using the Registry-like cohort (mean age: 24.4 years; mean ppFEV: 69.4 percentage points), TEZ/IVA increases median survival by an estimated 7.5 years.

CONCLUSIONS: Based on modeling, TEZ/IVA is projected to improve survival for F508del/F508del patients aged ≥12 years. Results were robust to alternative assumptions including reduction in rate of ppFEVdecline and use of a registry-like population.

Sponsored by Vertex Pharmaceuticals Incorporated

[1]Konstan. Lancet Respir Med