Phase 2 VIBRANT Trial: Verekitug Improves Nasal Polyps in Chronic Rhinosinusitis

Upstream Bio announced positive topline results from the phase 2 VIBRANT trial, which showed that verekitug provides significant improvement for chronic rhinosinusitis with nasal polyps (CRSwNP).1 The trial met its primary endpoint, with verekitug leading to a statistically significant and clinically meaningful reduction from baseline in endoscopic nasal polyp score.

“The improvements observed with verekitug, including durable nasal polyp reduction and symptom relief with a treatment potentially administered only four times per year, are encouraging,” said lead investigator Joseph Han, MD, professor in the department of otolaryngology & head and neck surgery and the chief for the division of allergy at Old Dominion University, Eastern Virginia Medical School, in a statement.1 “These results suggest verekitug could represent a meaningful advancement in the treatment of this chronically debilitating condition.”

Corticosteroids, surgery, and biologics can treat CRSwNP, characterized by a postnasal drip, nasal congestion, facial pressure or pain, and loss of smell or taste. However, post-surgical recurrence rates, reported to be between 18.2% and 60%, show that current treatments are not doing enough to manage uncontrolled symptoms that are impacting daily life.2,3

Preclinical studies have shown that verekitug can inhibit cytokine production from both CD4+ T cells and ILC2 cells and can completely suppress skin allergic reactions in a non-human primate model.1 This finding suggested that verekitug may be effective against multiple types of inflammation.

VIBRANT, a phase 2 randomized, placebo-controlled, parallel group clinical trial, assessed the efficacy and safety of verekitug, a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody that binds to the TSLP receptor and inhibits proinflammatory signaling, in adults with CRSwNP.1 The primary endpoint was the change in endoscopic nasal polyp score from baseline to week 24. Secondary endpoints included nasal congestion score, sinus opacification, difficulty with sense of smell, total symptom score, percentage of participants requiring systemic corticosteroids or nasal polyp surgery, and the time to first such interventions up to week 24.

The trial included participants who were receiving concurrent intranasal corticosteroid therapy. Investigators randomized 81 participants to either 100 mg of verekitug or a placebo subcutaneously every 12 weeks for 24 weeks.

The study met its primary endpoint, with verekitug providing a significant reduction from baseline in the endoscopic nasal polyp score of -1.8 (P < .0001) at week 24. The study also met secondary endpoints, with verekitug demonstrating a significant reduction from baseline in patient-reported nasal congestion score by -0.8 (P = .0003).

Furthermore, verekitug significantly improved sinus opacification (measured by the Lund-Mackay score), reduction in the need for systemic corticosteroid or nasal polyp surgery, and total symptom score. Overall, verekitug was well-tolerated with a consistent safety profile found in previous trials; the trial identified no serious adverse events.

“This is an important milestone in the development of verekitug. The VIBRANT trial results demonstrated statistically significant and clinically meaningful benefits with verekitug dosed every 12 weeks, positioning it to potentially advance the standard of care in the treatment of CRSwNP,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development at Upstream Bio, in a statement.1 “These results reinforce our earlier observations that verekitug’s high potency, achieved through targeting the TSLP receptor, has the potential to translate into clinical attributes distinct from those offered by any currently available therapy.”

Upstream Bio CEO Rand Sutherland, MD, said in the press release that verekitug has the potential to improve other respiratory diseases, including severe asthma.1

“As we prepare to report top-line data in severe asthma in the coming months, we are encouraged by these findings and remain committed to maximizing the opportunity to transform care with verekitug in multiple indications,” Sutherland said.1

Editors' note: The article previously stated VIBRANT was a phase 3 study. This is incorrect; it is a phase 2 trial.

References

1. Upstream Bio Reports Positive Top-Line Results from the Phase 2 VIBRANT Trial of Verekitug for the Treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). GlobeNewswire News Room. Published September 2, 2025. Accessed September 2, 2025. https://www.globenewswire.com/news-release/2025/09/02/3142434/0/en/Upstream-Bio-Reports-Positive-Top-Line-Results-from-the-Phase-2-VIBRANT-Trial-of-Verekitug-for-the-Treatment-of-Chronic-Rhinosinusitis-with-Nasal-Polyps-CRSwNP.html

2. Cavaliere C, Simonetta Masieri, Elona Begvarfaj, et al. Long-Term Perspectives on Chronic Rhinosinusitis with Nasal Polyps: Evaluating Recurrence Rates after Functional Endoscopic Sinus Surgery in the Biologics Era—A 5-Year Follow-Up Study. Journal of personalized medicine. 2024;14(3):297-297. doi:https://doi.org/10.3390/jpm14030297

3. Riva G, Tavassoli M, Cravero E, et al. Long-term evaluation of nasal polyposis recurrence: A focus on multiple relapses and nasal cytology. American Journal of Otolaryngology. 2022;43(2):103325. doi:https://doi.org/10.1016/j.amjoto.2021.103325