Early and Sustained Improvements in Sense of Smell With Tezepelumab Treatment in Patients With Chronic Rhinosinusitis With Nasal Polyps (WAYPOINT)

ABSTRACT Background Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting HRQoL and posing a safety hazard. Methods WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 weeks. Results Among 408 patients (tezepelumab [ n = 203]; placebo [ n = 205]), significant improvements with tezepelumab versus placebo in NPSD loss of smell item, UPSIT, and SNOT‐22 loss of smell/taste item scores were seen at week 4 (least‐squares mean [LSM] treatment difference [95% CI]: −0.36 [−0.46, −0.27]; 6.03 [4.72, 7.34]; and −1.01 [−1.22, −0.80], respectively) and week 52 (−1.01 [−1.18, −0.83]; 9.50 [7.84, 11.16]; and −1.90 [−2.20, −1.61]); all nominal p < 0.0001. Between‐treatment differences in daily NPSD loss of smell item score were evident from day 7 (LSM treatment difference: −0.08 [95% CI: −0.15, −0.02]; nominal p < 0.01). Improvements in NPSD loss of smell, UPSIT, and SNOT‐22 loss of smell/taste item scores were observed across multiple prespecified subgroups. Anosmia prevalence was lower with tezepelumab than placebo at week 4 (43.0% [ n/N = 64/149] vs. 80.3% [ n/N = 106/132]) and week 52 (31.5% [ n/N = 55/149] vs. 75.8% [ n/N = 100/132]). Conclusions Tezepelumab provides early and sustained improvements in the sense of smell among patients with uncontrolled CRSwNP.