Abstract Rationale Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with high symptom burden and a reduced quality of life. Sinonasal inflammation is largely driven by thymic stromal lymphopoietin (TSLP) and type 2 inflammatory mediators. Verekitug is a highly potent, fully human monoclonal antibody that targets the TSLP receptor. In the phase 2 VIBRANT trial (NCT06164704), treatment with 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. The objective of this analysis was to evaluate the effect of verekitug on type 2 inflammation biomarkers in the serum and nasal secretions. 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 post hoc analysis evaluated the median percent change from baseline (CFB) of inflammatory biomarkers in blood and nasal secretions over 24 weeks of verekitug treatment. Results The study randomized 81 participants (verekitug, n = 41; placebo, n = 40), of whom 74 participants (91.4%; verekitug, n = 38; placebo, n = 36) had blood eosinophils of ≥ 150 cells/µL at baseline. Baseline levels of blood eosinophils, and blood and nasal biomarkers, including eotaxin-3, interleukin (IL)-4, IL-13, IL-5, periostin, and thymus and activation-regulated cytokine (TARC), were generally balanced across treatment groups. Reductions in blood eosinophil measurements were greater at week 24 after treatment with verekitug (median percent CFB range, -59.6 -91.8 to 258.8) versus placebo (median percent CFB range, -18.1 -71.4 to 600.0). In addition, blood and nasal levels of eotaxin-3, periostin, IL-4, IL-13, and IL-5 had greater reductions at week 24 in participants receiving verekitug versus placebo (Table). Conclusions In participants with uncontrolled, severe CRSwNP, verekitug led to greater reduction of type 2 inflammatory biomarkers in blood and nasal secretions over 24 weeks than placebo treatment. This abstract is funded by: Upstream Bio, Inc., Waltham, MA, USA
Sivapalasingam et al. (Fri,) studied this question.