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
BACKGROUND:Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy. OBJECTIVE:This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial. METHODS:REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months. RESULTS:Of the 392 participants (male 54.8%; median age 7.2 y) who received at least 1 dose of treatment, 77.8% completed the 36-month active treatment. Mean adherence to treatment was high at 96.4%. Most participants (98.7%) experienced at least 1 treatment-emergent adverse event (TEAE); the majority were mild or moderate and decreased in frequency and severity over time. Most participants (94.6%) experienced at least 1 treatment-related TEAE. Local skin reactions were the most common treatment-related TEAE with the incidence decreasing from year 1 (87.8%) to year 3 (19.2%). Serious treatment-related TEAEs were reported in 2 participants. No specific safety signals were identified in the 14 participants enrolled with a history of severe anaphylaxis (Anaphylaxis Staging System grade 3). CONCLUSION:Consistent with previous phase 3 studies, long-term EPIT with VIASKIN peanut patch 250 μg was well tolerated with high adherence in peanut-allergic children aged 4 through 11 years (clinicaltrials.gov; NCT: NCT02916446).
