Verekitug Reduces Nasal Polyps in CRSwNP: Phase 2 Trial Results

A novel monoclonal antibody, verekitug, is demonstrating promising results in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), a condition characterized by inflammation of the sinuses and the development of soft, noncancerous growths in the nasal passages. Data presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting suggest that patients receiving verekitug experienced significant reductions in nasal polyp size and improvements in related symptoms over a 24-week period, compared to those receiving a placebo. This offers potential for a new therapeutic option in a disease area where current treatments often require frequent administration or are not universally effective.

Verekitug’s Mechanism and Trial Design

Verekitug distinguishes itself as the only known thymic stromal lymphopoietin (TSLP) receptor antagonist currently in development. TSLP is a key cytokine—a signaling molecule that promotes inflammation—involved in the development of CRSwNP. By blocking the TSLP receptor, verekitug aims to interrupt the inflammatory cascade driving the disease. The phase 2 VIBRANT trial, a double-blind, randomized study, evaluated the efficacy of 100 mg subcutaneous verekitug administered every 12 weeks for 24 weeks against placebo in 81 adults with severe, inadequately controlled CRSwNP. Participants had either a history of nasal polyp surgery or required systemic steroids for symptom management in the preceding 24 months, and exhibited significant nasal congestion and polyp burden at baseline.

The study enrolled patients with a history of nasal polyp surgery or exacerbations requiring systemic steroids, an endoscopic nasal polyp score (NPS) of 5 or higher, and notable nasal congestion. All participants continued their standard of care treatments alongside the study intervention. Researchers employed both a primary analysis, focusing on treatment policy, and a worst-observation-carried-forward (WOCF) analysis to assess the durability of the observed effects. The WOCF approach, as explained by Aaron Deykin, MD, chief medical officer and head of research and development at Upstream Bio, accounts for patients who may have needed to discontinue the study or require rescue medication, providing a more conservative estimate of treatment efficacy. Healio previously reported on initial findings from the trial.

Significant Improvements in Nasal Polyp Size and Symptoms

The results demonstrated a statistically significant improvement in endoscopic NPS from baseline to week 24 in the verekitug group compared to placebo, both in the primary analysis (-2.05 vs. -0.28; least-squares imply difference, -1.77; 95% CI, -2.51 to -1.03) and the WOCF analysis (-1.97 vs. -0.02; difference, -1.95; 95% CI, -2.66 to -1.24). Nasal congestion scores (NCS) also showed significant improvement with verekitug at week 24 in both analyses (primary: -1.53 vs. -0.76; difference, -0.77; 95% CI, -1.17 to -0.37; WOCF: -1.48 vs. -0.52; difference, -0.96; 95% CI, -1.37 to -0.55). Improvements in NCS were observed as early as week 2.

Beyond polyp size and congestion, verekitug also led to significant improvements in total symptom score (-4.69; 95% CI, -7.41 to -1.96), difficulty with sense of smell (-0.85; 95% CI, -1.29 to -0.42), and sinus disease extent and severity based on the Lund-Mackay score (-8.07; 95% CI, -10.23 to -5.92) in the primary analysis. Similar trends were observed in the WOCF analysis. Notably, a smaller proportion of patients in the verekitug group required nasal polyp surgery or systemic corticosteroids compared to the placebo group (7.3% vs. 25%), indicating a potential to reduce the need for more invasive interventions. The odds ratio for requiring surgery or steroids was 0.24 (95% CI, 0.06-0.94).

Safety Profile and Comparison to Tezepelumab

The safety profile of verekitug appeared favorable, with similar proportions of patients in both the verekitug and placebo groups reporting treatment-emergent adverse events (67.5% vs. 65%). Serious treatment-emergent adverse events were rare, and no patients discontinued treatment due to adverse events in the verekitug group. Dr. Deykin highlighted that the benign safety profile aligns with expectations, given the established safety of other TSLP-targeting therapies like tezepelumab. Healio notes that Dr. Deykin can be reached for further information.

In comparing verekitug to tezepelumab, another TSLP inhibitor approved for CRSwNP, Dr. Deykin suggested that the data are “remarkably, very strong and, in some cases, numerically better” than those reported for tezepelumab, even using the more conservative WOCF analysis. He emphasized that the results are particularly encouraging given the potential for a longer dosing interval with verekitug—every 12 weeks—which could improve patient convenience and adherence.

Next Steps: Phase 3 Trial and Broader Applications

Upstream Bio is planning a larger phase 3 trial to further evaluate the efficacy and safety of verekitug in CRSwNP, with enrollment expected to begin in early 2027. The company is also exploring the potential of verekitug in other inflammatory conditions, including severe asthma and chronic obstructive pulmonary disease (COPD). Ongoing analyses from a recent asthma study may inform the optimal dosing interval for verekitug—whether every 12 weeks or potentially every 24 weeks—and whether a higher dose could further enhance efficacy. The development of verekitug represents a significant step forward in the search for more effective and convenient treatments for CRSwNP and potentially other inflammatory diseases. MSN provides a broader glance at current health news.

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