Abstract Rationale Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by high symptom burden and reduced quality of life, with thymic stromal lymphopoietin (TSLP) playing a key role in driving inflammation. Verekitug is a highly potent, fully human monoclonal antibody targeting the TSLP receptor. The phase 2 VIBRANT trial (NCT06164704) demonstrated that verekitug led to statistically and clinically significant improvements in nasal polyp score (NPS) and nasal congestion symptoms over 24 weeks in participants with severe, uncontrolled CRSwNP versus placebo. Here, we report the effect of verekitug on lung function and Asthma Control Questionnaire-6 (ACQ-6) results in participants with comorbid asthma in the VIBRANT trial. Methods VIBRANT, a double-blind, placebo-controlled, phase 2 trial, randomized participants with severe, uncontrolled CRSwNP; endoscopic NPS (range: 0-8) ≥5; and previous endoscopic sinus surgery, or treatment with or intolerance to systemic corticosteroids to receive standard of care and either 100 mg subcutaneous verekitug or matching placebo every 12 weeks for 24 weeks. This sub-analysis employed a worst-observation-carried-forward approach. Results Of the 81 participants (verekitug, n = 41; placebo, n = 40) randomized in the primary analysis, 47 participants (58.0%; verekitug, n = 24; placebo, n = 23) had comorbid asthma. Baseline mean NPS and prebronchodilator forced expiratory volume in 1 second (FEV1) measurements were generally balanced between treatment arms (Table). Baseline FEV1 measurements suggested that overall baseline lung function was in the normal range. Over 24 weeks, treatment with verekitug led to statistically and clinically significant improvements in NPS in the subgroup of participants with comorbid asthma, similar to results from the primary analysis (Table). ACQ-6 scores were significantly improved at nearly twice the established minimal clinically significant improvement (0.5) following verekitug treatment at week 24 (Table). In contrast, there were no significant changes in prebronchodilator FEV1 (Table). Conclusions Participants with uncontrolled, severe CRSwNP enrolled in the VIBRANT trial with comorbid asthma had evidence of poorly controlled asthma symptoms by ACQ-6 but normal lung function at baseline as assessed by prebronchodilator FEV1. Verekitug administered every 12 weeks led to clinically significant improvements in both NPS and asthma symptom control, with no significant changes in FEV1. This abstract is funded by: Upstream Bio, Inc., Waltham, MA, USA
Sivapalasingam et al. (Fri,) studied this question.