Stratification value of nasal brushing arachidonate 15-lipoxygenase in stapokibart (CM310) treatment for patients with seasonal allergic rhinitis: Results from MERAK

Background: In the MERAK study, stapokibart (an anti-IL-4Rα mAb) as an add-on treatment did not demonstrate statistical significance in improving the primary endpoint in the overall population of patients with moderate-to-severe uncontrolled seasonal allergic rhinitis (SAR). Objective: This study aimed to investigate biomarkers that can identify patients who may experience enhanced benefit from the add-on use of stapokibart. Methods: Patients were randomized 1:1:1 to stapokibart 600–300 mg once weekly, stapokibart 600–300 mg every 2 weeks, or placebo once weekly for a 4-week treatment period. The primary endpoint was the mean change from baseline in the daily reflective total nasal symptom score during 2-week treatment. Levels of prespecified biomarkers involved in the pathogenesis of SAR were determined in nasal brushings, nasal secretions, and peripheral blood samples of participants. This post hoc analysis assessed the efficacy and safety of stapokibart based on biomarker-defined subgroups. Biomarker subgroups in which patients demonstrated statistically significant improvements in the primary efficacy endpoint after treatment with stapokibart (both dose regimens compared with placebo) were considered to be of stratification value. Results: Among the biomarkers we screened, baseline nasal brushing arachidonate 15-lipoxygenase ( ALOX15 ) was the only biomarker that met the predefined criteria of a biomarker with stratification significance. In patients with a baseline nasal brushing ALOX15 mRNA level ≥median, significant improvements in nasal and ocular symptoms and quality of life were seen in patients on stapokibart compared with those on placebo. However, in patients with a nasal brushing ALOX15 mRNA level <median, stapokibart did not provide additional benefits compared with placebo. Conclusion: In patients with moderate-to-severe uncontrolled SAR, those with higher nasal brushing ALOX15 mRNA levels benefit more from stapokibart as an add-on treatment in ameliorating symptoms and improving quality of life.