Efficacy and safety of tezepelumab in Japanese patients with chronic rhinosinusitis with nasal polyps: A subpopulation analysis of the randomized WAYPOINT study

OBJECTIVE: Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, effectively reduced polyp size in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Tezepelumab also reduced the need for nasal polyp surgery and systemic corticosteroids (SCS) in the phase 3 WAYPOINT study across 10 countries (including Japan). This descriptive subgroup analysis evaluated the efficacy and safety of tezepelumab in Japanese patients enrolled in the WAYPOINT study; no formal statistical hypothesis testing was performed. METHODS: Adults with severe uncontrolled CRSwNP were randomized to receive subcutaneous tezepelumab 210 mg or placebo once every 4 weeks. Evaluations included coprimary endpoints (change from baseline to week 52 in total Nasal Polyp Score [NPS] and bi-weekly mean Nasal Congestion Score [NCS]), key secondary endpoints (loss of smell score, total score on the SinoNasal Outcome Test 22-item [SNOT-22], and Lund-Mackay sinus score, and the need for nasal polyp surgery, SCS, or both), and safety outcomes in the Japanese population. RESULTS: Of the 408 patients overall, 33 were enrolled in Japan (tezepelumab, n = 17; placebo, n = 16). In the Japanese population, tezepelumab showed numerically favorable reductions versus placebo at week 52 in total NPS (least squares mean change from baseline [95% confidence interval] -2.30 [-3.17, -1.44] vs -1.24 [-2.13, -0.35]) and bi-weekly mean NCS (-1.63 [-2.01, -1.25] vs -1.08 [-1.47, -0.69]). Loss of smell, SNOT-22, and Lund-Mackay scores also showed numerically favorable reductions from baseline with tezepelumab compared with placebo. No Japanese patients receiving tezepelumab required nasal polyp surgery or SCS. Safety was consistent with the overall study population. CONCLUSION: In this exploratory subpopulation analysis, tezepelumab showed numerically favorable results compared with placebo across multiple endpoints and was well tolerated in Japanese patients with severe uncontrolled CRSwNP, with findings generally consistent with the overall WAYPOINT population. CLINICAL TRIAL REGISTRATION: NCT04851964 (Available at: https://clinicaltrials.gov/study/NCT04851964).