WS13.3 A new combination of CFTR modulators corrects processing and reduces chronic inhibition for F508del-CFTR

Post-hoc analysis of a randomized, double-blind, placebo-controlled, phase 3 study showed a significant difference in relative change from baseline in %-predicted FEV1 favouring the ataluren-treated group vs placebo in patients not using chronic inhaled tobramycin (non-TOBI). As exacerbations are key drivers of disease progression, the effect of ataluren on exacerbations in nmCF patients was studied. Methods: A post-hoc analysis was conducted on the effect of ataluren on exacerbations, as defined by the modified Fuchs’ criteria, in nonTOBI patients (N=146). Rates and rate ratio were estimated using a generalized linear model. Results: In non-TOBI patients, there was a significant 40% reduction in mean exacerbation rate at 48 weeks for patients on ataluren vs placebo (Table). Of non-TOBI patients receiving placebo, 53 of 74 (72%) patients were not on any inhaled antibiotics at baseline. Median time to first pulmonary exacerbation was ±280 days for ataluren vs ±165 days for placebo. There was a 50.7% reduction in mean duration of hospitalization in non-TOBI patients on ataluren vs placebo (3.3 days for ataluren vs 6.5 days for placebo).