286 X316761: a New Highly Efficacious Potentiator of Wild-Type and Mutant CFTR Channels

with only rare olfactory loss) and had largely stable SIT scores after infection.Figure 1.Spaghetti plot of change in quantitative olfactory function in adults with CF.Data were collected at baseline (before HEMT) and after 6 months (∼182 days) and 2 years (∼730 days) of HEMT.Treatment with HEMT through 2 years did not improve olfaction.Orange lines represent individuals homozygous for F508del and blue lines represent individuals heterozygous for F508del and a minimal function mutation.Conclusions: People with CF and CRS have olfactory impairment that does not improve with 2 years of ETI therapy.Quantitative olfactory function modestly worsened over time despite ETI, suggesting that olfactory dysfunction in adults may be irreversible and progresses over time.Participants reported modest improvements in olfactory-specific QOL that did not exceed clinical relevance thresholds.Further study of mechanisms of olfactory loss in people with CF and the impact of early intervention on preventing or improving olfactory dysfunction is warranted.